Murine oocyte destruction following intraovarian treatment with 3-methylcholanthrene or 7,12-dimethylbenz(a)anthracene: protection by alpha-naphthoflavone.
Bilateral or unilateral intraovarian injection with the polycyclic aromatic hydrocarbons 3-methylcholanthrene (3-MC), or 7,12-dimethylbenz(a)anthracene (DMBA) destroys oocytes in C57BL/6N and DBA/2N mice. The threshold for small oocyte destruction following bilateral intraovarian treatment with 3-MC was between 0.1 and 1 microgram/ovary in both DBA/2N amd C57BL/6N mice. After intraovarian treatment with DMBA, a more potent ovotoxin, the thresholds for small oocyte destruction were between 0.01 and 0.1 microgram/ovary. Calculated ED50's for small oocyte destruction following bilateral intraovarian treatment with 3-MC were C57BL/6N, 0.33 micrograms/ovary; DBA/2N, 1.02 micrograms/ovary--for DMBA the ED50's were C57BL/6N, 0.11 micrograms/ovary; DBA/2N, 0.03 micrograms/ovary. Unilateral intraovarian treatment also destroyed oocytes in the treated ovary. Treatment with intraperitoneal alpha-naphthoflavone (ANF), a competitive inhibitor of polycyclic aromatic hydrocarbon metabolism by microsomal monooxygenases, inhibited oocyte destruction. Intraovarian treatment with ANF decreased oocyte destruction produced by intraovarian DMBA. These data suggest that both 3-MC and DMBA are indirect acting ovotoxins requiring metabolic activation before oocyte destruction occurs. In addition, these data also suggest that the ovary contains the enzymes necessary to biotransform xenobiotics like 3-MC and DMBA to ovotoxic metabolites. Metabolic activation of xenobiotics to reactive products within the ovary may represent a special threat to the integrity of oocyte DNA.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001571:Benzoflavones / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D007839:Functional Laterality; D008748:Methylcholanthrene / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009865:Oocytes / Q000166:cytology* / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000473:pathology*
D001571:Benzoflavones; D005419:Flavonoids; D008748:Methylcholanthrene; D015127:9,10-Dimethyl-1,2-benzanthracene; C011512:alpha-naphthoflavone