Activation of proto-oncogenes in human and mouse lung tumors

Journal Article · Sat Jun 01 00:00:00 EDT 1991 · Environmental Health Perspectives; (United States)

DOI:https://doi.org/10.1289/ehp.9193145· OSTI ID:6052887

Reynolds, S H; Anderson, M W ^[1]

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1. National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)

Lung cancer is a leading cause of cancer-related deaths in several nations. Epidemiological studies have indicated that 85% of all lung cancer deaths and 30% of all cancer deaths in the US are associated with tobacco smoking. Various chemicals in tobacco smoke are thought to react with DNA and to ultimately yield heritable mutations. In an effort to understand the molecular mechanisms involved in lung tumorigenesis, the authors have analyzed proto-oncogene activation in a series of human lung tumors from smokers and spontaneously occurring and chemically induced lung tumors in mice. Approximately 86% of the human lung tumors and > 90% of the mouse lung tumors were found to contain activated oncogenes. ras Oncogenes activated by point mutations were detected in many of the human lung adenocarcinomas and virtually all of the mouse lung adenomas and adenocarcinomas. The mutation profiles of the activated K-ras genes detected in the chemically induced mouse lung tumors suggest that the observed mutations result from genotoxic effects of the chemicals. Comparison of the K-ras mutations observed in the human lung adenocarcinomas with mutation profiles observed in the mouse lung tumors suggest that bulky hydrophobic DNA adducts may be responsible for the majority of the mutations observed in the activated human K-ras genes. Other data indicate that approximately 20% of human lung tumors contain potentially novel transforming genes that may also be targets for mutagens in cigarette smoke.

• OSTI ID: 6052887
• Journal Information: Environmental Health Perspectives; (United States), Vol. 93; ISSN 0091-6765
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
DNA ADDUCTS
MOLECULAR BIOLOGY
ONCOGENES
CHEMICAL ACTIVATION
GENE MUTATIONS
LUNG CLEARANCE
LUNGS
MAN
MICE
TOBACCO SMOKES
ADDUCTS
AEROSOLS
ANIMALS
BODY
CLEARANCE
COLLOIDS
DISPERSIONS
EXCRETION
GENES
MAMMALS
MUTATIONS
ORGANS
PRIMATES
RESIDUES
RESPIRATORY SYSTEM
RODENTS
SMOKES
SOLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology