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Title: Activation of ras oncogenes preceding the onset of neoplasia

The identification of ras oncogenes in human and animal cancers including precancerous lesions indicates that these genes participate in the early stages of neoplastic development. Yet, these observations do not define the timing of ras oncogene activation in the multistep process of carcinogenesis. To ascertain the timing of ras oncogene activation, an animal model system was devised that involves the induction of mammary carcinomas in rats exposed at birth to the carcinogen nitrosomethylurea. High-resolution restriction fragment length polymorphism analysis of polymerase chain reaction-amplified ras sequences revealed the presence of both H-ras and K-ras oncogenes in normal mammary glands 2 weeks after carcinogen treatment and at least 2 months before the onset of neoplasia. These ras oncogenes can remain latent within the mammary gland until exposure to estrogens, demonstrating that activation of ras oncogenes can precede the onset of neoplasia and suggesting that normal physiological proliferative processes such as estrogen-induced mammary gland development may lead to neoplasia if the targeted cells harbor latent ras oncogenes.
Authors:
;  [1] ;  [2]
  1. (Squibb Institute for Medical Research, Princeton, NJ (USA))
  2. (Salk Institute, La Jolla, CA (USA))
Publication Date:
OSTI Identifier:
6155731
Resource Type:
Journal Article
Resource Relation:
Journal Name: Science (Washington, D.C.); (USA); Journal Volume: 248:4959
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; MAMMARY GLANDS; CARCINOMAS; NITROSOUREAS; CARCINOGENESIS; ESTROGENS; EXPERIMENTAL NEOPLASMS; ONCOGENES; ONCOGENIC TRANSFORMATIONS; POLYMERASES; BODY; CELL TRANSFORMATIONS; DISEASES; ENZYMES; GENES; GLANDS; HORMONES; NEOPLASMS; NITROSO COMPOUNDS; NUCLEOTIDYLTRANSFERASES; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PATHOGENESIS; PHOSPHORUS-GROUP TRANSFERASES; STEROID HORMONES; TRANSFERASES 560300* -- Chemicals Metabolism & Toxicology