henk van kranen - Academia.edu (original) (raw)
Papers by henk van kranen
Carcinogenesis, 1998
The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary... more The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the Apc Min mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in Apc Min mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/ mouse, 15 animals/group), but not of colon tumors in male Apc Min mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.
Value in Health, 2014
A647 month after of the surgery we applied EORTC questionnaires QLQ-C30, PR25, and IN-PATSAT32. T... more A647 month after of the surgery we applied EORTC questionnaires QLQ-C30, PR25, and IN-PATSAT32. The scores for each questionnaire were calculated according formulas and instruction in the EORTC Scoring Manual. We calculated mean and standard deviation for each score.
European journal of human genetics : EJHG, Jan 3, 2015
This study explored individuals' preferences for genetic testing for colorectal cancer (CRC) ... more This study explored individuals' preferences for genetic testing for colorectal cancer (CRC) in a screening situation and their willingness to participate in genetic testing for Lynch syndrome, familial adenomatous polyposis (FAP), and familial colorectal cancer (FCC). For that purpose, 532 respondents aged 55-65 years completed a Discrete Choice Experiment. Using panel latent class models, the preferences for two screening situation characteristics (the probability of being genetically predisposed and the probability of developing CRC) and screening test characteristics (the frequency of preventive colonoscopies and CRC survival) were estimated. Based on these preferences, respondents' willingness to participate in the three screening initiatives was estimated. Lower-educated respondents and respondents who express serious anxiety and worries found colonoscopy frequency and the probability of developing CRC relatively more important and survival relatively less important co...
Antonie Van Leeuwenhoek International Journal of General and Molecular Microbiology, May 1, 1981
(Micro)organisms which are pathogenic to men, like certain bacteria, viruses and protozoa, are ge... more (Micro)organisms which are pathogenic to men, like certain bacteria, viruses and protozoa, are generally present in faecal-polluted surface water. From a hygienic point of view various treatment processes have to be applied to prepare safe drinking water out of this raw water. Each separate treatment process has its own inactivation capacity for pathogenic as well as indicator microorganisms. These inactivation capacities depend on the treatment sheme applied, as listed in Table 1. With regard to the quality of raw water it is known that microbial numbers in the aquatic environment can change rapidly. Some average concentrations of pathogenic as well as indicator organisms are given in Table 2 to illustrate the level of faecal pollution in the river Rhine and Meuse. The overall removal capacity of treatment schemes as illustrated in Table l is estimated to be in the order of ___ 10 log units in practice. Differences in the capacity of specific treatment processes such as disinfection in removing indicator organisms and especially enteric viruses are levelled off in the total treatment scheme. Assuming a 10 log removal capacity, microbial numbers in raw water as presented in Table 2, are reduced to less than one microorganism per cubic meter.
Monographs in virology, Apr 16, 2015
Carcinogenesis, 1994
The PCR technique in combination with selective hybridization to mutation specific oligonucleotid... more The PCR technique in combination with selective hybridization to mutation specific oligonucleotides, is a widely used methodology for the detection of activating point mutations in ras oncogenes. In the present paper we demonstrate for the N-ras gene of the rat that processed pseudogenes do interfere with this method. A first indication for this interference came from the sequence analysis of cloned PCR fragments of exon 1, amplified with primers derived from previously reported exon sequences of the mouse N-ras gene. Between different clones originating from one PCR reaction, a marked sequence heterogeneity is observed and this is shown to be the result of the presence of at least two different processed pseudogenes of the rat N-ras gene. These two pseudogenes, together with the wildtype N-ras gene and a small 3' part of the unr gene, were eventually cloned and their genomic organization and nucleotide sequences determined. Furthermore, representative examples of the confounding effects of these pseudogenes on the screening for activating point mutations are presented. Taken together, our results demonstrate that intron-specific amplification is a prerequisite for the unambiguous detection of activating point mutations in the N-ras gene of the rat.
Nutrition and Cancer, Mar 1, 2003
Phytoestrogens, like isoflavonoids and lignans, have been postulated as possible colorectal cance... more Phytoestrogens, like isoflavonoids and lignans, have been postulated as possible colorectal cancer protective constituents. To investigate this hypothesis, two high-fiber sources rich in lignan precursors, i.e., rye bran and flaxseed, were tested for their ability to modulate intestinal tumor development in ApcMin mice. Test diets consisted of a control diet (a Western-style diet, adjusted for fiber and/or phytate content) supplemented with 5% flaxseed or 30% rye bran. Chemical analysis of diets and blood samples confirmed the enhanced systemic exposure of mice fed the test diets to the major lignan precursors, i.e., secoisolariciresinol and matairesinol. No statistically significant difference was observed in the incidence and multiplicity of small intestinal and colon tumors at terminal sacrifice between mice fed the control diet or the diet supplemented with 5% flaxseed. With the rye bran diet a statistically significant enhancement of the number of small intestinal tumors in female mice was observed. The number of colon tumors, however, was comparable between the control and rye bran-fed mice of either sex. Furthermore, no activating point mutations in the K-ras oncogene nor positive immunohistochemical staining for the p53 gene were observed in a set of 48 colon tumors. In conclusion, our results demonstrate that increased intake of lignan precursors from flaxseed or rye bran, administered in a Western-style diet, does not protect against intestinal tumor development in an appropriate animal model for intestinal neoplasia such as the ApcMin mice.
Genes, Chromosomes and Cancer, Jan 29, 2003
Serrated adenomas, hyperplastic polyps, and admixed hyperplastic/adenomatous polyps form a distin... more Serrated adenomas, hyperplastic polyps, and admixed hyperplastic/adenomatous polyps form a distinct group of colorectal tumors, the molecular genetic basis of which is still poorly understood. We describe a novel mouse model for serrated adenomas and mixed polyposis, here referred to as Sad (serrated adenomas), caused by a spontaneously risen splice site mutation in the murine Smad4 gene. The Sad chromosomal region was identified by genetic linkage and loss of heterozygosity (LOH) analysis. Subsequently, several candidate genes were investigated by expression and mutation analysis. By use of genetic linkage and LOH analysis, we mapped the Sad candidate to mouse chromosome 18, 44-48 cM, syntenic to human chromosome band 18q21. Within this chromosomal interval, the Smad2, Smad4, and Smad7 genes were analyzed for the presence of a disease-causing mutation in affected animals. A single nucleotide (nt) deletion was identified in the intron 5/exon 6 splice acceptor site of the Smad4 gene. The single base deletion results in a frameshift and an early termination codon through activation of a cryptic splice site 4 nt downstream in exon 6. The resulting mRNA is unstable, and the Sad mutation is thus likely to represent a null allele. Identification of a Smad4 mutation in the Sad mouse model provides further support for the involvement of the Smad genes, and thus the TGFB pathway, in the serrated/hyperplastic route to colorectal cancer.
Gene, 1987
The enzyme ornithine decarboxylase (ODC; EC 4.1.1.17) catalyses the first and rate-limiting step ... more The enzyme ornithine decarboxylase (ODC; EC 4.1.1.17) catalyses the first and rate-limiting step in polyamine biosynthesis. Its activity is markedly increased in rapidly growing or regenerating tissue and is subject to regulation by a variety of trophic and mitogenic stimuli. ODC is therefore believed to play an essential role in the onset of cellular proliferation. In a molecular-biological approach to investigate ODC regulation upon induction by tumor promoters in rat liver we isolated an almost full-length rat ODC cDNA clone of 2.4 kb (designated pODC.E10) from a cDNA library of testosterone-induced rat kidney poly(A)+ RNA. Characterization by restriction-endonuclease mapping and sequence analysis showed strong homology to mouse ODC cDNA sequences previously published [Gupta and Coffino, J. Biol. Chem. 260 (1985) 2941-2944; Kahana and Nathans, Proc. Natl. Acad. Sci. USA 82 (1985) 1673-1677; Hickok et al., Proc. Natl. Acad. Sci. USA 83 (1986) 594-598]. This homology is most pronounced in the 461-aa-spanning coding region, amounting to 94% and 97% at the DNA and protein levels, respectively. In the 423-nt 5' leader the rat-mouse homology (approx. 75%) is most pronounced in a region of about 175 nt directly upstream from the translational start site. The leader sequence also contains a perfect inverted repeat of 54 nt and ten additional upstream ATG triplets, which are all followed by nonsense codons before the initiating ATG. In the 633-nt 3' trailer region of pODC.E10 an additional polyadenylation signal is observed more than 300 nt upstream from the 3' end. Rat-mouse homology is about 80% up to this first polyadenylation signal and is considerably less thereafter. The presence of two alternate polyadenylation sites most likely accounts for the 3' size heterogeneity observed in the two ODC mRNAs of 2.1 and 2.6 kb, respectively. In rat liver both mRNAs are coordinately induced by different tumor promoters. Finally, Southern blot analysis of normal rat liver and rat hepatoma DNA revealed that rat ODC, as in other rodents, belongs to a multigene family.
International Archives of Occupational and Environmental Health, Sep 1, 1995
In the present study a cancer risk assessment of occupational exposure to cyclophosphamide (CP), ... more In the present study a cancer risk assessment of occupational exposure to cyclophosphamide (CP), a genotoxic carcinogenic antineoplastic agent, was car ried out following two approaches based on (1) data from an animal study and (2) data on primary and secondary tumors in CP-treated patients. D ata on the urinary excretion of CP in health care workers were used to estimate the uptake of CP, which ranged from 3.6 to 18 p.g/day. Based on data from an animal study, cancer risks were calculated for a health care worker with a body weight of 70 kg and a working period of 40 years, 200 days a year (linear extrapolation). The life time risks (70 years) of urinary bladder cancer in men and leukemias in men and women were found to be nearly the same and ranged from 95 to 600 per million. Based on the patient studies, cancer risks were cal culated by multiplication of the 10-year cumulative incidence per gram of C P in patients by the estimated mean total uptake in health care workers over 10 years, 200 days a year. The risk of leukemias in women over 10 years ranged from 17 to 100 per million using the secondary tum or data (linear extrapolation). Com para ble results were obtained for the risk of urinary bladder tumors and leukemias in men and women when pri mary tum or data were used. Thus, on an annual basis, cancer risks obtained from both the animal and the patient study were nearly the same and ranged from about 1.4 to 10 per million. In The Netherlands it is proposed that, for workers, a cancer risk per compound
Elsevier eBooks, 2001
Abstract Specific signal transduction pathways that regulate cell cycling, differentiation and ap... more Abstract Specific signal transduction pathways that regulate cell cycling, differentiation and apoptosis are found to be corrupted in skin cancers, e.g. the epidermal growth-stimulating Hedgehog pathway in basal cell carcinomas (BCC). Mutations in genes coding for proteins in these pathways lead to persistent disturbances which are passed along to daughter cells, e.g. mutations in the gene for the Patched (PTCH) protein in the Hedgehog pathway. UV radiation damages DNA and can cause such mutations, but thus far only the point mutations in P53 genes from squamous cell carcinomas and BCC, and in PTCH genes from BCC of xeroderma pigmentosum (XP) patients appear to be unambiguously attributable to solar UV radiation. Solar UVB radiation is most effective in causing these point mutations. Other forms of UV-induced genetical changes may, however, contribute to skin carcinogenesis with different wavelength dependencies.
Familial Cancer, Sep 25, 2012
, F. J. (2013). Contribution of bi-allelic germline MUTYH mutations to early-onset and familial c... more , F. J. (2013). Contribution of bi-allelic germline MUTYH mutations to early-onset and familial colorectal cancer and to low number of adenomatous polyps: case-series and literature review. Familial Cancer, 12(1), 43-50.
Nucleic Acids Research, 1988
Science of The Total Environment, Jul 1, 1980
ABSTRACT
European Journal of Cancer and Clinical Oncology, 1991
Journal of Virology, Sep 1, 1986
We have compared the capacities of the ElA regions of nononcogenic adenovirus type 5 (AdS) and hi... more We have compared the capacities of the ElA regions of nononcogenic adenovirus type 5 (AdS) and highly oncogenic Adl2 to cooperate with the EJ bladder carcinoma Ha-ras-1 oncogene in the transformation of primary baby rat kidney cells. Both ElA regions, when cotransfected with the Ha-ras oncogene, transformed the primary cells with a low frequency. Ad5 ElA plus Ha-ras-transformed cells differed in phenotype from cells transformed by Adl2 ElA plus Ha-ras. The cells expressing Ad5 ElA appeared highly transformed and practically failed to adhere to plastic. This phenotype may be due to the virtually complete absence of fibronectin gene expression in these cells. In contrast, the cells expressing Adl2 EIA were flatter and adhered to plastic, whereas fibronectin gene expression was reduced but not absent. The oncogenic potential of the two types of ElA plus ras-transformed cells was tested by their injection into both athymic nude mice and weanling syngeneic rats. The AdS EIA plus ras-transformed cells were found to be highly oncogenic in both animal species, whereas the Adl2 EIA plus ras-transformed cells were only weakly oncogenic in both syngeneic rats and nude mice. The difference in oncogenic potential of the Ad5 ElA plus ras-and the Adl2 ElA plus ras-transformed cells is discussed in terms of the different capacities of the AdS and Adl2 ElA-encoded proteins to modulate cellular gene expression.
Science of The Total Environment, Apr 1, 1981
ABSTRACI' m results of this surge~ led to the decision to extend this investigation to 19 cities.... more ABSTRACI' m results of this surge~ led to the decision to extend this investigation to 19 cities. Finally, preliminary results regarding the characterization of the organic genotoxic compounds, Dresent in drinking water, will be discussed.
Carcinogenesis, 1998
The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary... more The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the Apc Min mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in Apc Min mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/ mouse, 15 animals/group), but not of colon tumors in male Apc Min mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.
Value in Health, 2014
A647 month after of the surgery we applied EORTC questionnaires QLQ-C30, PR25, and IN-PATSAT32. T... more A647 month after of the surgery we applied EORTC questionnaires QLQ-C30, PR25, and IN-PATSAT32. The scores for each questionnaire were calculated according formulas and instruction in the EORTC Scoring Manual. We calculated mean and standard deviation for each score.
European journal of human genetics : EJHG, Jan 3, 2015
This study explored individuals' preferences for genetic testing for colorectal cancer (CRC) ... more This study explored individuals' preferences for genetic testing for colorectal cancer (CRC) in a screening situation and their willingness to participate in genetic testing for Lynch syndrome, familial adenomatous polyposis (FAP), and familial colorectal cancer (FCC). For that purpose, 532 respondents aged 55-65 years completed a Discrete Choice Experiment. Using panel latent class models, the preferences for two screening situation characteristics (the probability of being genetically predisposed and the probability of developing CRC) and screening test characteristics (the frequency of preventive colonoscopies and CRC survival) were estimated. Based on these preferences, respondents' willingness to participate in the three screening initiatives was estimated. Lower-educated respondents and respondents who express serious anxiety and worries found colonoscopy frequency and the probability of developing CRC relatively more important and survival relatively less important co...
Antonie Van Leeuwenhoek International Journal of General and Molecular Microbiology, May 1, 1981
(Micro)organisms which are pathogenic to men, like certain bacteria, viruses and protozoa, are ge... more (Micro)organisms which are pathogenic to men, like certain bacteria, viruses and protozoa, are generally present in faecal-polluted surface water. From a hygienic point of view various treatment processes have to be applied to prepare safe drinking water out of this raw water. Each separate treatment process has its own inactivation capacity for pathogenic as well as indicator microorganisms. These inactivation capacities depend on the treatment sheme applied, as listed in Table 1. With regard to the quality of raw water it is known that microbial numbers in the aquatic environment can change rapidly. Some average concentrations of pathogenic as well as indicator organisms are given in Table 2 to illustrate the level of faecal pollution in the river Rhine and Meuse. The overall removal capacity of treatment schemes as illustrated in Table l is estimated to be in the order of ___ 10 log units in practice. Differences in the capacity of specific treatment processes such as disinfection in removing indicator organisms and especially enteric viruses are levelled off in the total treatment scheme. Assuming a 10 log removal capacity, microbial numbers in raw water as presented in Table 2, are reduced to less than one microorganism per cubic meter.
Monographs in virology, Apr 16, 2015
Carcinogenesis, 1994
The PCR technique in combination with selective hybridization to mutation specific oligonucleotid... more The PCR technique in combination with selective hybridization to mutation specific oligonucleotides, is a widely used methodology for the detection of activating point mutations in ras oncogenes. In the present paper we demonstrate for the N-ras gene of the rat that processed pseudogenes do interfere with this method. A first indication for this interference came from the sequence analysis of cloned PCR fragments of exon 1, amplified with primers derived from previously reported exon sequences of the mouse N-ras gene. Between different clones originating from one PCR reaction, a marked sequence heterogeneity is observed and this is shown to be the result of the presence of at least two different processed pseudogenes of the rat N-ras gene. These two pseudogenes, together with the wildtype N-ras gene and a small 3' part of the unr gene, were eventually cloned and their genomic organization and nucleotide sequences determined. Furthermore, representative examples of the confounding effects of these pseudogenes on the screening for activating point mutations are presented. Taken together, our results demonstrate that intron-specific amplification is a prerequisite for the unambiguous detection of activating point mutations in the N-ras gene of the rat.
Nutrition and Cancer, Mar 1, 2003
Phytoestrogens, like isoflavonoids and lignans, have been postulated as possible colorectal cance... more Phytoestrogens, like isoflavonoids and lignans, have been postulated as possible colorectal cancer protective constituents. To investigate this hypothesis, two high-fiber sources rich in lignan precursors, i.e., rye bran and flaxseed, were tested for their ability to modulate intestinal tumor development in ApcMin mice. Test diets consisted of a control diet (a Western-style diet, adjusted for fiber and/or phytate content) supplemented with 5% flaxseed or 30% rye bran. Chemical analysis of diets and blood samples confirmed the enhanced systemic exposure of mice fed the test diets to the major lignan precursors, i.e., secoisolariciresinol and matairesinol. No statistically significant difference was observed in the incidence and multiplicity of small intestinal and colon tumors at terminal sacrifice between mice fed the control diet or the diet supplemented with 5% flaxseed. With the rye bran diet a statistically significant enhancement of the number of small intestinal tumors in female mice was observed. The number of colon tumors, however, was comparable between the control and rye bran-fed mice of either sex. Furthermore, no activating point mutations in the K-ras oncogene nor positive immunohistochemical staining for the p53 gene were observed in a set of 48 colon tumors. In conclusion, our results demonstrate that increased intake of lignan precursors from flaxseed or rye bran, administered in a Western-style diet, does not protect against intestinal tumor development in an appropriate animal model for intestinal neoplasia such as the ApcMin mice.
Genes, Chromosomes and Cancer, Jan 29, 2003
Serrated adenomas, hyperplastic polyps, and admixed hyperplastic/adenomatous polyps form a distin... more Serrated adenomas, hyperplastic polyps, and admixed hyperplastic/adenomatous polyps form a distinct group of colorectal tumors, the molecular genetic basis of which is still poorly understood. We describe a novel mouse model for serrated adenomas and mixed polyposis, here referred to as Sad (serrated adenomas), caused by a spontaneously risen splice site mutation in the murine Smad4 gene. The Sad chromosomal region was identified by genetic linkage and loss of heterozygosity (LOH) analysis. Subsequently, several candidate genes were investigated by expression and mutation analysis. By use of genetic linkage and LOH analysis, we mapped the Sad candidate to mouse chromosome 18, 44-48 cM, syntenic to human chromosome band 18q21. Within this chromosomal interval, the Smad2, Smad4, and Smad7 genes were analyzed for the presence of a disease-causing mutation in affected animals. A single nucleotide (nt) deletion was identified in the intron 5/exon 6 splice acceptor site of the Smad4 gene. The single base deletion results in a frameshift and an early termination codon through activation of a cryptic splice site 4 nt downstream in exon 6. The resulting mRNA is unstable, and the Sad mutation is thus likely to represent a null allele. Identification of a Smad4 mutation in the Sad mouse model provides further support for the involvement of the Smad genes, and thus the TGFB pathway, in the serrated/hyperplastic route to colorectal cancer.
Gene, 1987
The enzyme ornithine decarboxylase (ODC; EC 4.1.1.17) catalyses the first and rate-limiting step ... more The enzyme ornithine decarboxylase (ODC; EC 4.1.1.17) catalyses the first and rate-limiting step in polyamine biosynthesis. Its activity is markedly increased in rapidly growing or regenerating tissue and is subject to regulation by a variety of trophic and mitogenic stimuli. ODC is therefore believed to play an essential role in the onset of cellular proliferation. In a molecular-biological approach to investigate ODC regulation upon induction by tumor promoters in rat liver we isolated an almost full-length rat ODC cDNA clone of 2.4 kb (designated pODC.E10) from a cDNA library of testosterone-induced rat kidney poly(A)+ RNA. Characterization by restriction-endonuclease mapping and sequence analysis showed strong homology to mouse ODC cDNA sequences previously published [Gupta and Coffino, J. Biol. Chem. 260 (1985) 2941-2944; Kahana and Nathans, Proc. Natl. Acad. Sci. USA 82 (1985) 1673-1677; Hickok et al., Proc. Natl. Acad. Sci. USA 83 (1986) 594-598]. This homology is most pronounced in the 461-aa-spanning coding region, amounting to 94% and 97% at the DNA and protein levels, respectively. In the 423-nt 5' leader the rat-mouse homology (approx. 75%) is most pronounced in a region of about 175 nt directly upstream from the translational start site. The leader sequence also contains a perfect inverted repeat of 54 nt and ten additional upstream ATG triplets, which are all followed by nonsense codons before the initiating ATG. In the 633-nt 3' trailer region of pODC.E10 an additional polyadenylation signal is observed more than 300 nt upstream from the 3' end. Rat-mouse homology is about 80% up to this first polyadenylation signal and is considerably less thereafter. The presence of two alternate polyadenylation sites most likely accounts for the 3' size heterogeneity observed in the two ODC mRNAs of 2.1 and 2.6 kb, respectively. In rat liver both mRNAs are coordinately induced by different tumor promoters. Finally, Southern blot analysis of normal rat liver and rat hepatoma DNA revealed that rat ODC, as in other rodents, belongs to a multigene family.
International Archives of Occupational and Environmental Health, Sep 1, 1995
In the present study a cancer risk assessment of occupational exposure to cyclophosphamide (CP), ... more In the present study a cancer risk assessment of occupational exposure to cyclophosphamide (CP), a genotoxic carcinogenic antineoplastic agent, was car ried out following two approaches based on (1) data from an animal study and (2) data on primary and secondary tumors in CP-treated patients. D ata on the urinary excretion of CP in health care workers were used to estimate the uptake of CP, which ranged from 3.6 to 18 p.g/day. Based on data from an animal study, cancer risks were calculated for a health care worker with a body weight of 70 kg and a working period of 40 years, 200 days a year (linear extrapolation). The life time risks (70 years) of urinary bladder cancer in men and leukemias in men and women were found to be nearly the same and ranged from 95 to 600 per million. Based on the patient studies, cancer risks were cal culated by multiplication of the 10-year cumulative incidence per gram of C P in patients by the estimated mean total uptake in health care workers over 10 years, 200 days a year. The risk of leukemias in women over 10 years ranged from 17 to 100 per million using the secondary tum or data (linear extrapolation). Com para ble results were obtained for the risk of urinary bladder tumors and leukemias in men and women when pri mary tum or data were used. Thus, on an annual basis, cancer risks obtained from both the animal and the patient study were nearly the same and ranged from about 1.4 to 10 per million. In The Netherlands it is proposed that, for workers, a cancer risk per compound
Elsevier eBooks, 2001
Abstract Specific signal transduction pathways that regulate cell cycling, differentiation and ap... more Abstract Specific signal transduction pathways that regulate cell cycling, differentiation and apoptosis are found to be corrupted in skin cancers, e.g. the epidermal growth-stimulating Hedgehog pathway in basal cell carcinomas (BCC). Mutations in genes coding for proteins in these pathways lead to persistent disturbances which are passed along to daughter cells, e.g. mutations in the gene for the Patched (PTCH) protein in the Hedgehog pathway. UV radiation damages DNA and can cause such mutations, but thus far only the point mutations in P53 genes from squamous cell carcinomas and BCC, and in PTCH genes from BCC of xeroderma pigmentosum (XP) patients appear to be unambiguously attributable to solar UV radiation. Solar UVB radiation is most effective in causing these point mutations. Other forms of UV-induced genetical changes may, however, contribute to skin carcinogenesis with different wavelength dependencies.
Familial Cancer, Sep 25, 2012
, F. J. (2013). Contribution of bi-allelic germline MUTYH mutations to early-onset and familial c... more , F. J. (2013). Contribution of bi-allelic germline MUTYH mutations to early-onset and familial colorectal cancer and to low number of adenomatous polyps: case-series and literature review. Familial Cancer, 12(1), 43-50.
Nucleic Acids Research, 1988
Science of The Total Environment, Jul 1, 1980
ABSTRACT
European Journal of Cancer and Clinical Oncology, 1991
Journal of Virology, Sep 1, 1986
We have compared the capacities of the ElA regions of nononcogenic adenovirus type 5 (AdS) and hi... more We have compared the capacities of the ElA regions of nononcogenic adenovirus type 5 (AdS) and highly oncogenic Adl2 to cooperate with the EJ bladder carcinoma Ha-ras-1 oncogene in the transformation of primary baby rat kidney cells. Both ElA regions, when cotransfected with the Ha-ras oncogene, transformed the primary cells with a low frequency. Ad5 ElA plus Ha-ras-transformed cells differed in phenotype from cells transformed by Adl2 ElA plus Ha-ras. The cells expressing Ad5 ElA appeared highly transformed and practically failed to adhere to plastic. This phenotype may be due to the virtually complete absence of fibronectin gene expression in these cells. In contrast, the cells expressing Adl2 EIA were flatter and adhered to plastic, whereas fibronectin gene expression was reduced but not absent. The oncogenic potential of the two types of ElA plus ras-transformed cells was tested by their injection into both athymic nude mice and weanling syngeneic rats. The AdS EIA plus ras-transformed cells were found to be highly oncogenic in both animal species, whereas the Adl2 EIA plus ras-transformed cells were only weakly oncogenic in both syngeneic rats and nude mice. The difference in oncogenic potential of the Ad5 ElA plus ras-and the Adl2 ElA plus ras-transformed cells is discussed in terms of the different capacities of the AdS and Adl2 ElA-encoded proteins to modulate cellular gene expression.
Science of The Total Environment, Apr 1, 1981
ABSTRACI' m results of this surge~ led to the decision to extend this investigation to 19 cities.... more ABSTRACI' m results of this surge~ led to the decision to extend this investigation to 19 cities. Finally, preliminary results regarding the characterization of the organic genotoxic compounds, Dresent in drinking water, will be discussed.