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PMID: 8170982 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

N-nitroso-N-methylurea-induced rat mammary tumors arise from cells with preexisting oncogenic Hras1 gene mutations.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 9 ·1994-04-26 ·Pages 3749-53

Cha RS, Thilly WG, Zarbl H

Abstract

GGA to GAA mutations in the 12th codon of the Hras gene are frequently observed in rat mammary tumors induced by N-nitroso-N-methylurea (NMU). We developed an assay to measure point mutations present in tissues at a frequency of 10(-5) and have now applied this assay to measure the specific G to A transition of the Hras gene in rat mammary epithelium. We find that (i) 70% of untreated rats contain detectable levels of Hras mutants; (ii) these mutants are clustered within the gland as sectors in a manner consistent with their origin as a mutation arising during early organ development; and (iii) treatment with a carcinogenic dose of NMU did not result in a significant increase in the number of such mutants, the fraction of organ sectors with mutant cells, or the fraction of animals containing detectable levels of ras mutants. We conclude that the NMU-induced mammary tumors carrying the G to A transition at the 12th codon of the Hras gene arose from preexisting ras mutants and that an independent effect of NMU was directly or indirectly responsible for tumor formation.

Related Genes
Hras
MeSH Terms
Animals Female Genes, ras Mammary Neoplasms, Experimental/chemically induced,genetics Methylnitrosourea Mutation Oncogenes Rats Rats, Inbred F344
Chemicals
Methylnitrosourea
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Cha R S
Division of Toxicology, Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.
Thilly W G
Zarbl H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.9.3749
Published
1994-04-26
Pages
3749-53
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC43659
Subset
IM
Grants
NIEHS NIH HHS · P01ES05622-02 · United States
NIEHS NIH HHS · P01ESO3926-08 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.9.3749 PMC Full Text View journal details
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