NON-LINEAR DOSE-RESPONSE RELATIONSHIP FOR BINDING OF CARCINOGEN BENZO(A)PYRENE TO RAT-LIVER DNA INVIVO

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (3) , 575-578
Abstract
With radioactive compounds of high specific activity, the binding of carcinogens to DNA can be measured with doses that are ineffective in long-term studies. The binding of 3H-benzo(a)pyrene to liver DNA of adult male rats was determined 50 h after a single i.p. injection of doses between 40 .mu.g/kg and 4 mg/kg. The dose-response relationship is linear up to 1 mg/kg, shows a step toward 2 mg/kg and gives a shallow linear slope above that value. The observed binding ranges from 1.7-180 nmol benzo(a)pyrene/mole DNA phosphate. The nonlinearity could be due to an induction of metabolizing enzymes. The microsomal aryl hydrocarbon hydroxylase activity increases significantly 24 h after a single dose of 4 mg/kg and 48 h aftr doses of 2 and 4 mg/kg, but no induction is found with 1 mg/kg. Binding from an equimolar dose is 35 times lower than found on mouse skin DNA and 300 times lower than that of N,N-dimethylnitrosamine in rat liver. A good correlation exists to the respective tumor formation in long-term studies.

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