Oocyte destruction by polycyclic aromatic hydrocarbons is not linked to the inducibility of ovarian aryl hydrocarbon (benzo(a)pyrene) hydroxylase activity in (DBA/2N X C57BL/6N) F1 X DBA/2N backcross mice.
The role of the Ah locus and ovarian aryl hydrocarbon (benzo(a)pyrene) hydroxylase activity (AHH, EC 1.14.14.1) in ovotoxicity produced by the polycyclic aromatic hydrocarbons benzo(a)pyrene (BP), 3-methylcholanthrene (3-MC), and 7,12-dimethylbenz(a)anthracene (DMBA) was explored in Ah-responsive and Ah-nonresponsive (DBA/2N X C57BL/6N) F1 X DBA/2N backcross (F1 X D2) mice. The F1 X D2 backcross mice were phenotyped by zoxazolamine muscle paralysis time and separated into responsive and nonresponsive groups. Basal ovarian AHH activity was similar in both responsive and nonresponsive phenotypes (0.2 fluorescence units/mg/30 minutes). After treatment with one of the three polycyclic hydrocarbons (100 mg/kg, IP), ovarian AHH activity was induced only in the responsive F1 X D2 phenotype (0.4 fluorescence units/mg/30 minutes), demonstrating that inducibility of ovarian AHH activity is associated with the Ahb allele. Although responsive and nonresponsive backcross mice difference in inducibility of ovarian AHH activity, no difference was observed in the rate of, or sensitivity to, primordial oocyte destruction by the three tested polycyclic hydrocarbons. At 15 days after treatment with a single injection of BP (100 mg/kg, IP), approximately 30% of the primordial oocytes were destroyed in both responsive and nonresponsive F1 X D2 mice. The time course for oocyte destruction over the 15-day observation period was similar in both phenotypes. DMBA (100 mg/kg, IP) destroyed all of the primordial oocytes between 9 and 12 days after treatment with similar time courses in both responsive and nonresponsive phenotypes. Treatment with 3-MC (100 mg/kg, IP) destroyed approximately 40% and 70% of the primordial oocytes in responsive and nonresponsive F1 X D2 mice, respectively. Although ovarian metabolism of polycyclic hydrocarbons is necessary for ovotoxicity, oocyte destruction is not linked to the Ah locus. Sensitivity to, or the time course of, ovotoxicity by polycyclic aromatic hydrocarbons most likely reflects the biological sum of the processes of metabolic activation, detoxication, and repair and cannot be simply represented by a single enzymatic assay such as ovarian AHH activity.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001579:Benzopyrene Hydroxylase / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D009865:Oocytes / Q000187:drug effects*; D010053:Ovary / Q000201:enzymology*; D010063:Ovum / Q000187:drug effects*; D011083:Polycyclic Compounds / Q000633:toxicity*; D015049:Zoxazolamine
D011083:Polycyclic Compounds; D008748:Methylcholanthrene; D015049:Zoxazolamine; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases