Abstract

Primordial oocyte destruction by polycyclic aromatic hydrocarbons requires metabolic activation of the polycyclic hydrocarbon to an ovotoxic metabolite. The first and perhaps subsequent step(s) in the metabolism of polycyclic aromatic hydrocarbons to the proximate ovotoxin occurs via a microsomal cytochrome P-450-dependent monooxygenase. The role of aryl hydrocarbon (benzo[ a]pyrene) hydroxylase (AHH, EC 1.14.14.2) in activation of polycyclic hydrocarbons to ovotoxic products was studied in 11 inbred and two F 1 heterozygote murine strains. The polycyclic aromatic hydrocarbon responsive C57BL/6N and C57BL/6J mice had two- to threefold increases in ovarian AHH activity after polycyclic hydrocarbon treatment. The polycyclic aromatic hydrocarbon nonresponsive DBA/2N and DBA/2J mice had no change in ovarian AHH activity after similar polycyclic hydrocarbon treatment. The polycyclic aromatic hydrocarbon responsive C57BL/6N and C57BL/6J mice had more rapid primordial oocyte destruction after polycyclic hydrocarbon treatment than the nonresponsive DBA/2N and DBA/2J mice. The (DBA/2N)(C57BL/6N)F 1 and (DBA/2J)(C57BL/6J)F 1 mice were responsive to polycyclic hydrocarbons with two- to threefold increases in ovarian AHH activity after treatment, however, the rate of oocyte destruction was similar to that observed in the nonresponsive DBA/2N and DBA/2J mice. Survey of seven additional inbred strains of mice failed to demonstrate a strong correlation between either absolute ovarian AHH activity or fold induction of ovarian AHH activity and oocyte destruction. Similarly, treatment with 2,3,7,8-tetrachlorodibenzo- p-dioxin, a potent inducer of ovarian AHH activity in both polycyclic hydrocarbon responsive and nonresponsive strains, did not alter the rate of oocyte destruction after treatment with benzo[ a]pyrene or 3-methylcholanthrene. Although metabolic activation of polycyclic aromatic hydrocarbons to an ovotoxin is necessary for primordial oocyte destruction, strain differences in sensitivity to oocyte destruction reflect the biological sum of activation, detoxification, and repair. Therefore, differences in ovarian AHH activity or inducibility may not reflect differences in oocyte destruction after polycyclic hydrocarbon treatment.

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