Sensitivity of subpopulations of mouse skin papillomas to malignant conversion by urethane or 4-nitroquinoline N-oxide - PubMed (original) (raw)
. 1990 Feb 1;50(3):653-7.
Affiliations
- PMID: 2105160
Sensitivity of subpopulations of mouse skin papillomas to malignant conversion by urethane or 4-nitroquinoline N-oxide
H Hennings et al. Cancer Res. 1990.
Abstract
Papillomas induced in SENCAR mice by initiation with 7,12-dimethylbenz(a)anthracene and promotion by treatment for 10-12 weeks with 12-O-tetradecanoylphorbol-13-acetate (TPA) convert to malignancy at a low frequency. The rate of malignant conversion can be increased by either (a) promoting with TPA for a shorter duration or (b) treatment of papilloma-bearing mice with certain genotoxic chemicals, such as 4-nitroquinoline N-oxide (4-NQO) or urethane. The spontaneous conversion rate of papillomas promoted by 5 weeks of TPA exposure is severalfold higher than that of papillomas arising later during TPA promotion. Here, we compared the sensitivity to the converting agents 4-NQO and urethane of papillomas promoted by TPA for either 5, 10, or 20 weeks. In the mice promoted for 5 weeks with TPA, the already high spontaneous conversion frequency was increased 2.5 times by 4-NQO. A 2-fold increase was found after 10 weeks of TPA promotion. In contrast, no increase was seen with 4-NQO exposure begun after 20 weeks of TPA promotion. Similar results were found with urethane as converting agent. The sensitivity of the papillomas induced by short-term TPA treatment to induced conversion remains high even after a 16-week period without TPA treatment; when urethane exposure was delayed until week 21 after TPA promotion for weeks 1-5, a 2.4-fold increase in the conversion frequency was observed.
Similar articles
- Genetic alterations cooperate with v-Ha-ras to accelerate multistage carcinogenesis in TG.AC transgenic mouse skin.
Owens DM, Spalding JW, Tennant RW, Smart RC. Owens DM, et al. Cancer Res. 1995 Jul 15;55(14):3171-8. Cancer Res. 1995. PMID: 7606738 - Malignant conversion, the first stage in progression, is distinct from phorbol ester promotion in mouse skin.
Hennings H. Hennings H. Basic Life Sci. 1991;57:31-9; discussion 39-42. doi: 10.1007/978-1-4684-5994-4_4. Basic Life Sci. 1991. PMID: 1814291 - The paradigm of two-stage carcinogenesis: a critical attitude.
Iversen OH, Astrup EG. Iversen OH, et al. Cancer Invest. 1984;2(1):51-60. doi: 10.3109/07357908409020286. Cancer Invest. 1984. PMID: 6423216 Review. No abstract available. - The high-risk benign tumor: evidence from the two-stage skin cancer model and relevance for human cancer.
Glick A, Ryscavage A, Perez-Lorenzo R, Hennings H, Yuspa S, Darwiche N. Glick A, et al. Mol Carcinog. 2007 Aug;46(8):605-10. doi: 10.1002/mc.20345. Mol Carcinog. 2007. PMID: 17538943 Review.
Cited by
- Loss of expression of transforming growth factor beta in skin and skin tumors is associated with hyperproliferation and a high risk for malignant conversion.
Glick AB, Kulkarni AB, Tennenbaum T, Hennings H, Flanders KC, O'Reilly M, Sporn MB, Karlsson S, Yuspa SH. Glick AB, et al. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6076-80. doi: 10.1073/pnas.90.13.6076. Proc Natl Acad Sci U S A. 1993. PMID: 7687059 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Medical