Initiation, promotion, initiation experiments with radon and cigarette smoke: Lung tumors in rats

Technical Report · Thu Feb 01 04:00:00 EST 1990

OSTI ID:6701613

Moolgavkar, S H

Much recent attention has focused on the recessive oncogenesis model according to which inactivation of both alleles of a tumor suppressor gene (anti-oncogene) leads to cancer. Over the past decade Dr. Moolgavkar has been involved in the development and testing of a two-mutation model for carcinogenesis, which may be viewed as a mathematical generalization of the recessive oncogenesis model. In a series of papers this model has been shown to be consistent with a large body of epidemiologic and experimental data. Thus, the current project funded under the auspices of DOE, is part of a much larger program. The goals of this larger program are: the mathematical development of the two-mutation model for application to various epidemiologic and experimental data sets; investigation of the statistical properties of the model and development of software for fitting the model to various data sets, including cohort and case-control data in epidemiology. Directly relevant to the radon program, we have completed an analysis of radon-induced lung tumors in rats within the context of the two-mutation model. We found that the model described the data well. The results indicate that fractionation of exposure increased the lifetime probability of tumor. Examination of the parameters of the model suggests that the effect of fractionation can be explained by the relative effects of radon daughters on the mutation rates and on the kinetics of growth of initiated cells. The first mutation rate is very strongly dependent upon the rate of exposure to radon daughters, the second mutation rate much less so, suggesting that the nature of the two mutational events is different.

• Research Organization: Fred Hutchinson Cancer Research Center, Seattle, WA (USA)
• Sponsoring Organization: DOE/ER
• DOE Contract Number: FG06-88ER60657
• OSTI ID: 6701613
• Report Number(s): DOE/ER/60657-3; ON: DE90016124
• 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.
AEROSOLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL MODELS
BODY
CARCINOGENESIS
COLLOIDS
DAUGHTER PRODUCTS
DISEASES
DISPERSIONS
DOCUMENT TYPES
ELEMENTS
FLUIDS
GASES
GENES
ISOTOPES
LUNGS
MAMMALS
NEOPLASMS
NONMETALS
ONCOGENES
ORGANS
PATHOGENESIS
PROGRESS REPORT
RADON
RARE GASES
RATS
RESIDUES
RESPIRATORY SYSTEM
RISK ASSESSMENT
RODENTS
SMOKES
SOLS
TOBACCO PRODUCTS
TOBACCO SMOKES
TOXICITY
VERTEBRATES