Risk assessment and multiple stages in radiation carcinogenesis

Conference · Fri Jan 01 04:00:00 EST 1988

OSTI ID:6744898

Burns, F J; Sawey, M J; Hosselet, S; Garte, S J

Epithelial cancers are induced in rat skin by ionizing radiation in a manner that is consistent with the dual action (i.e., 2 alterations) hypothesis of radiation effects on DNA. This hypothesis states that 2 initial alterations are necessary to start a normal cell on the pathway to career. The expected cancer yield, Y(D,t), as a function of dose, D, and time, t, has the form Y(D,t) = C(aLD + BD/sup 2/)t,/sup n/, where L is the average LET, D is the radiation dose, a, B are constants and n is an integer. In accordance with multistage theory, n was assumed to be 2 on the basis of the best fit to cancer onset data. Values for a and B were estimated from cancer induction experiments in rat skin exposed to monoenergetic electrons (LET = 0.34 keV/..mu..) or argon ions (LET = 125 keV/..mu..). The repair halftime for carcinogenic alterations was found in split dose protocols to be 3.5 +- 1.0 hrs for electron radiation and >24 hrs for argon ions. As an approach to identifying cancer-relevant DNA alterations, skin tumor DNA was analyzed for oncogene activation. K-ras and c-myc oncogenes were activated in highly anaplastic rat skin cancers, whereas only one of these oncogenes, usually c-myc, was activated in squamous cell carcinomas and in comparatively benign basal cell carcinomas. 18 refs., 6 figs.

• Research Organization: New York Univ., NY (USA). Inst. of Environmental Medicine
• DOE Contract Number: FG02-87ER60539
• OSTI ID: 6744898
• Report Number(s): DOE/ER/60539-4; CONF-8809137-3; ON: DE89001805
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
BIOLOGICAL RADIATION EFFECTS
BODY
CARCINOGENESIS
DISEASES
DNA
DOSE-RESPONSE RELATIONSHIPS
FUNCTIONS
GENES
IONIZING RADIATIONS
MAMMALS
NEOPLASMS
NUCLEIC ACIDS
ONCOGENES
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
RADIATION EFFECTS
RADIATIONS
RADIOINDUCTION
RATS
RISK ASSESSMENT
RODENTS
SKIN
VERTEBRATES