Liver DNA alkylation after a single carcinogenic dose of dimethylnitrosamine to newborn and adult CFW Swiss mice.
N-nitrosodimethylamine N-demethylase activity, DNA alkylation, capacity for O6-methylguanine repair and cell proliferation were measured in livers of newborn and adult CFW mice after a single carcinogenic dose of DMNA. DNA alkylation was found in newborn and adult mouse livers but it was significantly higher in the newborn. 6- and 7-methyl substitutions of guanine were identified by HPLC analysis in newborn and in adult mouse livers. Metabolic 14C incorporation into adenine and guanine was observed only in liver DNA of newborns. O6-methylguanine levels were higher in newborn than adult mice after a single i.p. dose of [14C]DNMA. Liver DNA repair capacity measured as O6-meG-DNA methyltransferase was higher in adults than in newborns. De novo liver DNA synthesis was more inhibited by DMNA pretreatment in newborn than in adult mice. The relationship between these parameters and the greater neonatal liver tumor susceptibility is discussed.
Coccia
P
P
Laboratory for Enzyme Research, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Salmona
M
M
Diomede
L
L
Citti
L
L
Mariani
L
L
Romano
M
M
D000478:Alkylation; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D019392:Cytochrome P-450 CYP2E1; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D004128:Dimethylnitrosamine / Q000493:pharmacokinetics / Q000494:pharmacology*; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism
D006147:Guanine; D004247:DNA; C008449:O-(6)-methylguanine; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D004128:Dimethylnitrosamine