Nitrosodimethylamine metabolism in rat ovaries. Interactions of its metabolites with nucleic acids and proteins.
N-Nitrosodimethylamine (NDMA) was metabolized by ovarian slices of noninbred Sprague-Dawley rats (200-250 g body wt, to CO2 and to reactive metabolites that bind covalently to nucleic acids. That ability was about 10 or 5 times smaller than the one observed in liver slices, respectively. Both ovarian microsomes and mitochondria were able to biotransform NDMA to formaldehyde and to reactive metabolites that bind covalently to proteins. Formaldehyde formation by microsomes was significantly higher than that by ovarian mitochondria but of the same order of magnitude. Ability to lead to covalent binding to proteins in microsomes was not significantly different from that in the respective mitochondrial fraction. DNA isolated from ovarian slices activating NDMA revealed the presence of the altered bases 7-methylguanine (7-MeGua) and O6-methylguanine (O6-MeGua) resulting from NDMA reactive metabolites' attack. Results suggest potential, mutagenic, carcinogenic and reproductive risks derived from women's exposure to NDMA present in tobacco smoke, food, beverages, workplace or other environmental sources.
Díaz Gómez
M I
MI
Centro de Investigaciones Toxicológicas, CEITOX, CITEFA/CONICET, Buenos Aires, Argentina.
Tamayo
D
D
Castro
J A
JA
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004247:DNA / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000378:metabolism* / Q000633:toxicity; D005260:Female; D005557:Formaldehyde / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains
D005557:Formaldehyde; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D004128:Dimethylnitrosamine