Ha-ras oncogene activation in mammary glands of N-methyl-N-nitrosourea-treated rats genetically resistant to mammary adenocarcinogenesis

Journal Article · Sat Feb 01 04:00:00 EST 1992 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.89.3.1001· OSTI ID:5677750

Lu, Shijiang; Archer, M C ^[1]

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1. Univ. of Toronto, Ontario (Canada)

A single dose of N-methyl-N-nitrosourea given to sexually immature female Buf/N rats produces a high incidence of mammary adenocarcinomas. A large percentage of these tumors contain the Ha-ras oncogene, activated by a G {yields} A transition at the second nucleotide of codon 12. Copenhagen rats, on the other hand, are completely resistant to mammary tumor induction by a number of carcinogens, including N-methyl-N-nitrosourea. Here the authors show, using a sensitive method involving PCR, that codon 12 Ha-ras mutations occur in the mammary glands of both Buf/N and Copenhagen rats 30 days after N-methyl-N-nitrosourea treatment. These mutations were evenly distributed among individual mammary glands and were present in purified mammary epithelial cells. In Buf/N rats, the fraction of cells containing a mutated Ha-ras allele increased by a factor of 10-100 between 30 and 60 days, whereas in Copenhagen rats, there was no such increase during this time period. They conclude that the resistance of the Copenhagen rat to mammary carcinogenesis is not due to a defect in initiation but rather appears to be due to the inability of cells containing a mutated ras allele to undergo sustained clonal expansion.

• OSTI ID: 5677750
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 89:3; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AUTORADIOGRAPHY
BIOLOGICAL EFFECTS
BODY
CARBONIC ACID DERIVATIVES
CARCINOGENESIS
DNA
GENES
GENETIC EFFECTS
GLANDS
MAMMALS
MAMMARY GLANDS
METABOLIC ACTIVATION
METHYL NITROSOUREA
MOLECULAR BIOLOGY
MUTAGENS
NITROSO COMPOUNDS
NUCLEIC ACIDS
ONCOGENES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
RATS
RODENTS
SENSITIVITY
TUMOR CELLS
VERTEBRATES