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Ovarian Aryl Hydrocarbon Hydroxylase Activity and Primordial Oocyte Toxicity of Polycyclic Aromatic Hydrocarbons in Mice

Biochemical Pharmacology Section, Laboratory of Chemical Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute [S. S. T.], and Developmental Pharmacology Branch, National Institute of Child Health and Human Development [D. R. M.], NIH, Bethesda, Maryland 20014

Mouse ovarian aryl hydrocarbon hydroxylase (AHH, EC 1.14.14.2) activity was measured in control mice and in DBA/2N (hereafter called D2) and C57BL/6N (hereafter called B6) mice treated with 3-methylcholanthrene (MC). Basal ovarian AHH activity was similar in both strains (3 pmol/mg/min). Ovarian AHH was induced 2- to 3-fold in B6 mice after MC treatment, while no change was observed in similarly treated D2 mice. Primordial oocytes of both D2 and B6 mice were destroyed by the carcinogenic polycyclic aromatic hydrocarbons (PAH), MC, benzo(a)pyrene (BP), and 7,12-dimethylbenz(a)anthracene (DMBA), but not by the noncarcinogens, pyrene, -naphthoflavone, and ß-naphthoflavone. The rate of primordial oocyte destruction after PAH administration was faster in responsive B6 mice than in nonresponsive D2 mice. After a single i.p. injection of PAH (80 mg/kg), 50% of the oocytes were destroyed by the following times: DMBA, 1 day for B6, 2 days for D2; MC, between 2 and 3 days for B6, 6 days for D2; BP, between 2 and 3 days for B6, 12 days for D2. Dose-response curves of DMBA, MC, and BP also indicated greater primordial oocyte toxicity in responsive B6 mice than in nonresponsive D2 mice. The threshold dose for oocyte destruction 5 days after PAH injection was: DMBA, <1 mg/kg for B6, <2.5 mg/kg for D2; MC, <5 mg/kg for B6, 80 mg/kg for D2; BP, <5 mg/kg for B6, 80 mg/kg for D2. In MC-treated D2B6F₁ x D2 backcross mice, PAH-inducible ovarian AHH activity and rapid primordial oocyte toxicity cosegregated with inducible hepatic AHH activity. Primordial oocyte toxicity was blocked by simultaneous treatment with -naphthoflavone. The relative toxicity of the carcinogens to primordial oocytes in both D2 and B6 mice was DMBA > MC > BP.

¹ To whom requests for reprints should be addressed, at Reproductive Toxicology Unit, Pregnancy Research Branch, National Institute of Child Health and Human Development, NIH, Building 10, Room 13N266, Bethesda, Md. 20014.

Received 3/ 5/79. Accepted 5/31/79.

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