Ole Vang | Roskilde University (original) (raw)
Papers by Ole Vang
A series of new usnic acid ketamine compounds [1-8] and their oxime analogues [9-12] were synthes... more A series of new usnic acid ketamine compounds [1-8] and their oxime analogues [9-12] were synthesized by reacting (+)-usnic acid with various amines and subsequent treatment with hydroxylamine hydrochloride. They were evaluated on the human glioblastoma-astrocytoma cell line (U87MG) by a MTT assay for cell viability in vitro. The ketamine-derivatives (Schiff bases) show significant cytotoxicity on U87MG cells. A novel N-heterocyclic derivative (1,4-diazepine) showed an interesting tautomeric structure and displayed more activity on cancer cell line than (+)-usnic acid itself.
Pharmacology & Toxicology, Jun 1, 1993
The biotransformation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) and the protein ... more The biotransformation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) and the protein binding of PhIP and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was studied using microsomes from PCB-pretreated or untreated male rats of the strains, Wistar, Fischer and Sprague-Dawley. The microsomal monooxygenases, P450IA1 and IA2, which are important for the biotransformation of heterocyclic amines, were quantified by immunoblots. The two metabolites detected, 2-amino-1-methyl-6-(4'-hydroxyphenyl)imidazo[4,5-b]pyridine (4'OH-PhIP) and 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N2-OH-PhIP) were formed in similar amounts whereas no minor metabolites were found in our highly sensitive radiochemical assay. Irrespective of the rat strain used, pretreatment with PCB significantly induced both the activation and the detoxication in all three rat strains. Except for a significantly higher concentration of P450IA2 in microsomes from control and PCB induced Wistar rats, no major differences between the strains were found.
Carcinogenesis, 1996
Ingestion of cruciferous vegetables may prevent chemically induced carcinogenesis by their influe... more Ingestion of cruciferous vegetables may prevent chemically induced carcinogenesis by their influence on specific cytochrome P450 enzymes (CYP) and phase II drug metabolizing enzymes in humans and rodents. Thus CYP enzymes are involved in transformation of procarcinogens, mutagens, steroid hormones and a large variety of other endogenous and exogenous components. In order to learn more about the influence of cruciferous vegetables on drug metabolizing enzymes in man two CYP enzymes previously suggested to be induced by vegetables were selected in an in vivo experiment in humans. Sixteen healthy non-smoking subjects, two females and 14 males, were exposed to three different types of diets and afterwards assayed for CYP1A2 catalysed caffeine metabolites and for CYP2E1 catalysed 6-hydroxylation of chlorzoxazone. Further, 2-hydroxyoestrone:16a-hydroxyoestrone ratios were determined in urine by means of a monoclonal antibody-based enzyme immunoassay. The three dietary periods were: (A) a customary home diet; (B) a 6 day standard diet avoiding well-known dietary inducers and inhibitors of CYP; (C) a 12 day dietary supplement to the standard diet of 500 g/day broccoli. The average 6-hydroxychlorzoxazone:chlorzoxazone ratio decreased by 21% (P < 0.05) after diet B compared with diet A in a 2 h plasma sample after ingestion of 500 mg chlorzoxazone. The ratio increased by 19% after diet C, however, this was not statistically significant. The caffeine metabolic ratio (CMR) was determined in urine 6 h after ingestion of 100 mg caffeine. The mean CMR increased by 5.5% when changing from diet A to diet B. When shifting to diet C the mean CMR increased a further 19% (P < 0.0005). The average 2-hydroxyoestrone:16cchydroxyoestrone ratio decreased by 13% when comparing diet A with diet B. Daily broccoli intake increased the ratio by 29.5% (P < 0.05). A low correlation of CMR with the 2-hydroxyoestrone:16a-hydroxyoestrone ratio indicates that human CYP1A2 and other CYP enzymes involved in oestrone 2-hydroxylation are induced by dietary broccoli. On the other hand, the catalytic activity of CYP2E1 is not affected to the same degree by dietary broccoli.
European Journal of Cancer Prevention, Oct 1, 1997
Purinergic Signalling, 2008
Early experiments in the 1960's will be described leading to the purinergic neurotransmission hyp... more Early experiments in the 1960's will be described leading to the purinergic neurotransmission hypothesis proposed in 1972. The influence of publications by key figures such as Andrew Szent-Györgyi, Pamela Holton, Robert Berne, Mike Rand and Jack Eccles is recognised. Unfortunately, the hypothesis was regarded with scepticism by many for the next 25 years and stories of this resistance will be recounted. The cloning of receptors for purines and pyrimidines in the early 1990's was an important turning point in the acceptance of the hypothesis and the important contributions of many outstanding scientists will be related. Current strong interest in the pathophysiological roles of purinergic signalling and exploration of the therapeutic potential for a number of disease conditions will be discussed.
CRC Press eBooks, Sep 22, 2005
The plasticizer di(2-ethylhexyl)phthalate (DEHP) exhibits antiandrogenic effects in perinatally e... more The plasticizer di(2-ethylhexyl)phthalate (DEHP) exhibits antiandrogenic effects in perinatally exposed male rats. Di(2-ethylhexyl) adipate (DEHA) and diisononyl phthalate (DINP) are currently being evaluated as potential substitutes for DEHP, but similarities in structure and metabolism of DEHP with DEHA and DINP have led to the hypothesis that similarities in action may also exist. Pregnant Wistar rats were gavaged during gestation and lactation with vehicle, DEHP (300 or 750 mg/kg bodyweight per day), DINP (750 mg/kg bodyweight per day), DEHP (750 mg/kg bodyweight per day) in combination with DEHA (400 mg/kg bodyweight per day), or DEHP (300 mg/kg bodyweight per day) in combination with DINP (750 mg/kg bodyweight per day). DINP and DEHP were both shown to reduce testicular testosterone production ex vivo and testosterone levels in testes and plasma of male fetuses at gestation day 21, indicating a similar mechanism of action for DINP and DEHP. Additionally, plasma LH levels in ma...
Natural Products for Cancer Chemoprevention, 2020
Throughout this book the power of combination chemoprevention is highlighted. Even individual age... more Throughout this book the power of combination chemoprevention is highlighted. Even individual agents that function by virtue of pleiotropic mechanisms of action portray a combination effect. In this final chapter, we offer a brief perspective on the concept of combining numerous (e.g., 10–25) dietary agents for the creation of a cocktail capable of mediating a broad-based cancer chemopreventive response. The challenges of logically and systematically founding a cocktail comprised of 10–25 dietary chemopreventive components functioning in an additive or synergistic manner are addressed. Obviously, this is no mean task. Some technological advances are necessary, such as creating in vitro systems engineered to encompass several hallmarks of cancer, and animal models that generically correlate with the genesis of human cancer. Nonetheless, as illustrated by the cogent, on point contributions presented in this book, over the past several decades, we have already acquired the knowledge and skill necessary for accomplishing this vast undertaking. Given the current day morbidity and mortality associated with malignant metastatic cancer, and future projections of even greater devastation, all of humanity would benefit by a holistic approach utilizing the tools provided to us by Nature.
The Journal of Immunology, 2020
A series of new usnic acid ketamine compounds [1-8] and their oxime analogues [9-12] were synthes... more A series of new usnic acid ketamine compounds [1-8] and their oxime analogues [9-12] were synthesized by reacting (+)-usnic acid with various amines and subsequent treatment with hydroxylamine hydrochloride. They were evaluated on the human glioblastoma-astrocytoma cell line (U87MG) by a MTT assay for cell viability in vitro. The ketamine-derivatives (Schiff bases) show significant cytotoxicity on U87MG cells. A novel N-heterocyclic derivative (1,4-diazepine) showed an interesting tautomeric structure and displayed more activity on cancer cell line than (+)-usnic acid itself.
Pharmacology & Toxicology, Jun 1, 1993
The biotransformation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) and the protein ... more The biotransformation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) and the protein binding of PhIP and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was studied using microsomes from PCB-pretreated or untreated male rats of the strains, Wistar, Fischer and Sprague-Dawley. The microsomal monooxygenases, P450IA1 and IA2, which are important for the biotransformation of heterocyclic amines, were quantified by immunoblots. The two metabolites detected, 2-amino-1-methyl-6-(4'-hydroxyphenyl)imidazo[4,5-b]pyridine (4'OH-PhIP) and 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N2-OH-PhIP) were formed in similar amounts whereas no minor metabolites were found in our highly sensitive radiochemical assay. Irrespective of the rat strain used, pretreatment with PCB significantly induced both the activation and the detoxication in all three rat strains. Except for a significantly higher concentration of P450IA2 in microsomes from control and PCB induced Wistar rats, no major differences between the strains were found.
Carcinogenesis, 1996
Ingestion of cruciferous vegetables may prevent chemically induced carcinogenesis by their influe... more Ingestion of cruciferous vegetables may prevent chemically induced carcinogenesis by their influence on specific cytochrome P450 enzymes (CYP) and phase II drug metabolizing enzymes in humans and rodents. Thus CYP enzymes are involved in transformation of procarcinogens, mutagens, steroid hormones and a large variety of other endogenous and exogenous components. In order to learn more about the influence of cruciferous vegetables on drug metabolizing enzymes in man two CYP enzymes previously suggested to be induced by vegetables were selected in an in vivo experiment in humans. Sixteen healthy non-smoking subjects, two females and 14 males, were exposed to three different types of diets and afterwards assayed for CYP1A2 catalysed caffeine metabolites and for CYP2E1 catalysed 6-hydroxylation of chlorzoxazone. Further, 2-hydroxyoestrone:16a-hydroxyoestrone ratios were determined in urine by means of a monoclonal antibody-based enzyme immunoassay. The three dietary periods were: (A) a customary home diet; (B) a 6 day standard diet avoiding well-known dietary inducers and inhibitors of CYP; (C) a 12 day dietary supplement to the standard diet of 500 g/day broccoli. The average 6-hydroxychlorzoxazone:chlorzoxazone ratio decreased by 21% (P < 0.05) after diet B compared with diet A in a 2 h plasma sample after ingestion of 500 mg chlorzoxazone. The ratio increased by 19% after diet C, however, this was not statistically significant. The caffeine metabolic ratio (CMR) was determined in urine 6 h after ingestion of 100 mg caffeine. The mean CMR increased by 5.5% when changing from diet A to diet B. When shifting to diet C the mean CMR increased a further 19% (P < 0.0005). The average 2-hydroxyoestrone:16cchydroxyoestrone ratio decreased by 13% when comparing diet A with diet B. Daily broccoli intake increased the ratio by 29.5% (P < 0.05). A low correlation of CMR with the 2-hydroxyoestrone:16a-hydroxyoestrone ratio indicates that human CYP1A2 and other CYP enzymes involved in oestrone 2-hydroxylation are induced by dietary broccoli. On the other hand, the catalytic activity of CYP2E1 is not affected to the same degree by dietary broccoli.
European Journal of Cancer Prevention, Oct 1, 1997
Purinergic Signalling, 2008
Early experiments in the 1960's will be described leading to the purinergic neurotransmission hyp... more Early experiments in the 1960's will be described leading to the purinergic neurotransmission hypothesis proposed in 1972. The influence of publications by key figures such as Andrew Szent-Györgyi, Pamela Holton, Robert Berne, Mike Rand and Jack Eccles is recognised. Unfortunately, the hypothesis was regarded with scepticism by many for the next 25 years and stories of this resistance will be recounted. The cloning of receptors for purines and pyrimidines in the early 1990's was an important turning point in the acceptance of the hypothesis and the important contributions of many outstanding scientists will be related. Current strong interest in the pathophysiological roles of purinergic signalling and exploration of the therapeutic potential for a number of disease conditions will be discussed.
CRC Press eBooks, Sep 22, 2005
The plasticizer di(2-ethylhexyl)phthalate (DEHP) exhibits antiandrogenic effects in perinatally e... more The plasticizer di(2-ethylhexyl)phthalate (DEHP) exhibits antiandrogenic effects in perinatally exposed male rats. Di(2-ethylhexyl) adipate (DEHA) and diisononyl phthalate (DINP) are currently being evaluated as potential substitutes for DEHP, but similarities in structure and metabolism of DEHP with DEHA and DINP have led to the hypothesis that similarities in action may also exist. Pregnant Wistar rats were gavaged during gestation and lactation with vehicle, DEHP (300 or 750 mg/kg bodyweight per day), DINP (750 mg/kg bodyweight per day), DEHP (750 mg/kg bodyweight per day) in combination with DEHA (400 mg/kg bodyweight per day), or DEHP (300 mg/kg bodyweight per day) in combination with DINP (750 mg/kg bodyweight per day). DINP and DEHP were both shown to reduce testicular testosterone production ex vivo and testosterone levels in testes and plasma of male fetuses at gestation day 21, indicating a similar mechanism of action for DINP and DEHP. Additionally, plasma LH levels in ma...
Natural Products for Cancer Chemoprevention, 2020
Throughout this book the power of combination chemoprevention is highlighted. Even individual age... more Throughout this book the power of combination chemoprevention is highlighted. Even individual agents that function by virtue of pleiotropic mechanisms of action portray a combination effect. In this final chapter, we offer a brief perspective on the concept of combining numerous (e.g., 10–25) dietary agents for the creation of a cocktail capable of mediating a broad-based cancer chemopreventive response. The challenges of logically and systematically founding a cocktail comprised of 10–25 dietary chemopreventive components functioning in an additive or synergistic manner are addressed. Obviously, this is no mean task. Some technological advances are necessary, such as creating in vitro systems engineered to encompass several hallmarks of cancer, and animal models that generically correlate with the genesis of human cancer. Nonetheless, as illustrated by the cogent, on point contributions presented in this book, over the past several decades, we have already acquired the knowledge and skill necessary for accomplishing this vast undertaking. Given the current day morbidity and mortality associated with malignant metastatic cancer, and future projections of even greater devastation, all of humanity would benefit by a holistic approach utilizing the tools provided to us by Nature.
The Journal of Immunology, 2020