Oncogene activation in spontaneous and chemically induced rodent tumors: implications for risk analysis

Journal Article · Wed Jun 01 00:00:00 EDT 1988 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.1289/ehp.8878175· OSTI ID:6210934

Reynolds, S H; Stowers, S J; Patterson, R M; Maronpot, R R; Anderson, M W

The validity of rodent tumor end points in assessing the potential hazards of chemical exposure to humans is a somewhat controversial but very important issue since most chemicals are classified as potentially hazardous to humans on the basis of long-term carcinogenesis studies in rodents. The ability to distinguish between genotoxic, cytotoxic, or receptor-mediated promotion effects of chemical treatment would aid in the interpretation of rodent carcinogenesis data. Activated oncogenes in spontaneously occurring and chemically induced rodent tumors were examined and compared as one approach to determine the mechanism by which chemical treatment caused an increased incidence of rodent tumors. Different patterns of activated oncogenes were found not only in spontaneous versus chemically induced mouse liver tumors but also in a variety of spontaneous rat tumors versus chemically induced rat lung tumors. In the absence of cytotoxic effects, it could be argued that the chemicals in question activated protooncogenes by a direct genotoxic mechanism. These results provided a basis for the analysis of activated oncogenes in spontaneous and chemically induced rodent tumors to provide information at a molecular level to aid in the extrapolation of rodent carcinogenesis data to human risk assessment.

• Research Organization: National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)
• OSTI ID: 6210934
• Journal Information: Environ. Health Perspect.; (United States), Vol. 78
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
CARCINOGENESIS
RISK ASSESSMENT
ONCOGENES
CHEMICAL ACTIVATION
CARCINOGENS
EXTRAPOLATION
LIVER
MAN
MICE
MUTATIONS
NEOPLASMS
ANIMALS
BODY
DIGESTIVE SYSTEM
DISEASES
GENES
GLANDS
MAMMALS
NUMERICAL SOLUTION
ORGANS
PATHOGENESIS
PRIMATES
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550200 - Biochemistry