The pineal hormone melatonin inhibits DNA-adduct formation induced by the chemical carcinogen safrole in vivo.
Melatonin inhibits DNA-adduct formation induced by the chemical carcinogen safrole in a dose-dependent manner. Total DNA-adduct formation after in vivo administration of 300 mg/kg safrole measured by 32P-postlabeling analysis of carcinogen-modified DNA in rat liver was 36,751 +/- 2290 counts/min/10 micrograms DNA. Coadministration of 300 mg/kg safrole with either 0.2 mg/kg (low dose) or 0.4 mg/kg (high dose) melatonin reduced DNA-adduct formation induced by safrole to 22,182 +/- 987 counts/min/10 micrograms DNA and 462 +/- 283 counts/min/10 micrograms DNA, respectively. Circulating melatonin concentrations at the termination of the study in safrole, low melatonin and high melatonin groups were 50 +/- 8, 3140 +/- 430 and 10,040 +/- 2610 pg/ml serum, respectively. The results suggest that melatonin protects against safrole associated DNA damage.
Tan
D X
DX
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762.
Pöeggeler
B
B
Reiter
R J
RJ
Chen
L D
LD
Chen
S
S
Manchester
L C
LC
Barlow-Walden
L R
LR
D000818:Animals; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012451:Safrole / Q000378:metabolism* / Q000494:pharmacology
D004247:DNA; D008550:Melatonin; D012451:Safrole