THE PINEAL HORMONE MELATONIN INHIBITS DNA-ADDUCT FORMATION INDUCED BYTHE CHEMICAL CARCINOGEN SAFROLE IN-VIVO

Melatonin inhibits DNA-adduct formation induced by the chemical carcin ogen safrole in a dose-dependent manner. Total DNA-adduct formation af ter in vivo administration of 300 mg/kg safrole measured by P-32-postl abeling analysis of carcinogen-modified DNA in rat liver was 36 751 +/ - 2290 counts/min/10 mug DNA. Coadministration of 300 mg/kg safrole wi th either 0.2 mg/kg (low dose) or 0.4 mg/kg (high dose) melatonin redu ced DNA-adduct formation induced by safrole to 22 182 +/- 987 counts/m in/10 mug DNA and 462 +/- 283 counts/min/10 mug DNA, respectively. Cir culating melatonin concentrations at the termination of the study in s afrole, low melatonin and high melatonin groups were 50 +/- 8, 3140 +/ - 430 and 10 040 +/- 2610 pg/ml serum, respectively. The results sugge st that melatonin protects against safrole associated DNA damage.