Journal Article

<i>ras</i> gene mutations are absent in NMU-induced mammary carcinomas from aging rats

Todd A. Thompson, Jill D. Haag and Michael N. Gould

in Carcinogenesis

Volume 21, issue 10, pages 1917-1922
Published in print October 2000 | ISSN: 0143-3334
Published online October 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.10.1917
ras gene mutations are absent in NMU-induced mammary carcinomas from aging rats

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Carcinoma induction in the rat mammary carcinogenesis model is age dependent. In this study, mammary cancer susceptibility and ras gene activation were investigated in rats exposed to N-methyl-N-nitrosourea (NMU) at 2, 6, 8 and 15 months. Animals were resistant to NMU-induced mammary tumor development when exposed at 6 and 8 months of age, whereas a significant number of mammary carcinomas developed in animals exposed to NMU at 2 and 15 months of age. G35→A35 activating mutations in the Harvey ras gene were found only in mammary carcinomas from rats exposed to NMU at 2 months of age, but not in tumors that developed in animals exposed to NMU at 15 months of age. No G35→A35 activating mutations were present in the Kirsten ras gene of any of the mammary tumors. Additional analysis of exons 1 and 2 of the Harvey ras gene from mammary carcinomas that developed in animals exposed to NMU at 15 months of age did not reveal any other activating mutations in this gene. In mammary carcinomas from animals exposed to NMU at 2 months of age, the frequency of mammary carcinomas with mutations in the Harvey ras gene was independent of the time from which the tumor first appeared. Therefore, age at the time of carcinogen exposure plays a critical role in both breast cancer susceptibility and the molecular events that contribute to mammary carcinoma development.

Keywords: DMBA, 7,12-dimethylbenz[a]anthracene; NMU, N-methyl-N-nitrosourea; RFLP, restriction fragment length polymorphism.

Journal Article.  3777 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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