Document Detail

Quantitating the frequency of initiation and cH-ras mutation in in situ N-methyl-N-nitrosourea-exposed rat mammary gland.
MedLine Citation:
PMID:  2007094     Owner:  NLM     Status:  MEDLINE    
Mammary carcinogenesis is a multistep process consisting minimally of initiation and promotion/progression stages. The rate-limiting stage in the carcinogenesis process is undetermined but can in part be addressed by estimating the frequency of initiation, a heritable early event. Here, we use an in vivo limiting dilution transplantation assay to estimate initiation frequency in a rat mammary epithelial stem-like cell population that was exposed in situ to 50 mg/kg N-methyl-N-nitrosourea (NMU) administered i.v. We estimate that this dose resulted in the killing of 65% of exposed mammary cells. Known numbers of cells surviving NMU exposure were grafted into fat-pads of recipient rats in which the cells grew and differentiated into structurally and functionally normal mammary glands. Recipient rats were hormonally manipulated to provide maximal promotion of initiated cells. Mammary carcinomas developing at graft sites were quantitated over a 2-year period. Based on these results, we estimate that at least 1 surviving NMU-exposed mammary cell in 7,200 was initiated. Seventeen % of these graft site carcinomas had an activated H-ras oncogene with a G to A mutation in codon 12. This suggests that at least 1 mammary cell in 43,000 was mutated in this fashion by in situ exposure to NMU. These data suggest that cH-ras represents approximately 1 of 5 of the initiation events produced by NMU exposure of rat mammary glands.
R Zhang; J D Haag; M N Gould
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research     Volume:  2     ISSN:  1044-9523     ISO Abbreviation:  Cell Growth Differ.     Publication Date:  1991 Jan 
Date Detail:
Created Date:  1991-05-01     Completed Date:  1991-05-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9100024     Medline TA:  Cell Growth Differ     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1-6     Citation Subset:  IM    
Department of Human Oncology, University of Wisconsin-Madison 53792.
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MeSH Terms
Base Sequence
Cell Survival / drug effects
Gene Expression Regulation, Neoplastic / physiology
Genes, ras / drug effects,  genetics*
Mammary Neoplasms, Experimental / chemically induced,  genetics*
Methylnitrosourea / pharmacology
Molecular Sequence Data
Mutation / drug effects,  genetics*
Grant Support
Reg. No./Substance:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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