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Oocyte destruction by polycyclic aromatic hydrocarbons.

D R Mattison, K Shiromizu, M S Nightingale

    American Journal of Industrial Medicine
    |January 1, 1983
    PubMed
    Summary
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    Polycyclic aromatic hydrocarbons harm oocytes by forming toxic metabolites in the ovary. Measuring specific metabolite formation, not general enzyme activity, better predicts reproductive toxicity in different species.

    Area of Science:

    • Environmental Toxicology
    • Reproductive Toxicology
    • Biochemistry

    Background:

    • Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants.
    • PAHs can cause oocyte destruction, a process requiring ovarian metabolism.
    • Current assays for PAH metabolism do not accurately predict species-specific toxicity.

    Purpose of the Study:

    • To identify better predictors of PAH-induced ovotoxicity.
    • To investigate the role of specific metabolic pathways in PAH reproductive toxicity.
    • To use benzo(a)pyrene as a model compound for studying ovarian metabolic processing.

    Main Methods:

    • Utilized benzo(a)pyrene as a probe for ovarian metabolic processing.
    • Analyzed the formation of specific metabolites along the benzo(a)pyrene metabolic pathway.

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  • Compared metabolite formation rates with observed ovotoxicity.

    • Main Results:

    • The rate of formation of 7,8-dihydrodiol-9,10-epoxide metabolites correlates with ovotoxicity.
    • General aryl hydrocarbon hydroxylase (AHH) assays are poor predictors of PAH ovotoxicity.
    • Ovarian metabolic processing of benzo(a)pyrene involves a complex, multi-step pathway.

    Conclusions:

    • The rate of specific metabolite formation, particularly 7,8-dihydrodiol-9,10-epoxide, is a key determinant of PAH ovotoxicity.
    • Understanding the full metabolic pathway is crucial for predicting reproductive toxicity.
    • This metabolic pathway serves as a model for studying factors influencing reproductive toxicity, including activation, detoxification, and repair mechanisms.