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Chromatographic Analyses of 3-Methylcholanthrene Metabolism in Adult and Fetal Mice and the Occurrence of Conjugating Enzymes in the Fetus¹

Department of Pathology, Chest Disease Research Institute, Kyoto University, Sakyo-ku, Kyoto 606, Japan

Adult pregnant mice were given i.v. injections of [³H]3-methylcholanthrene (20 µCi in 1.1 µg/mouse) or [¹⁴C]3-methylcholanthrene (1.0 µCi in 48 µg/mouse). Ethanol extracts of their tissues were chromatographed on Sephadex LH-20. Three groups of 3-methylcholanthrene metabolites were obtained: one group as yet unidentified, one containing the hydrocarbon and hydroxylated derivatives, and a third consisting of conjugated metabolites from the treated adult mice and their fetuses. The conjugated metabolites in tissues and in bile were separated into two fractions; one was acted on by ß-glucuronidase and to a lesser extent by arylsulfatase, and the other was resistant to these enzymes but completely susceptible to acid hydrolysis. The hydrolysis resulted in altered chromatographic behavior characteristic of the hydroxy compounds, which also appear in tissue. The enzyme-resistant conjugates were predominant in brain, muscle, and lung, and the enzyme-labile conjugates were predominant in the kidney, liver, and bile of adult mice. These conjugated metabolites were also demonstrated in fetal mice; some appeared in the fetus as early as the thirteenth day of gestation, the most immature fetus so far examined. The resistant group was predominant in the early developmental stages of the fetus and the susceptible group was increased in the excretory organs such as the kidney, liver, and contents of the intestinal tract as the fetuses approached term.

Transplacental transfer of conjugated metabolites from the mother to the fetus did not take place, although the parent 3-methylcholanthrene and its nonconjugated metabolites were transferred. We therefore assume that drug-metabolizing enzymes, including hydroxylases and conjugases, are active in the fetal mouse tissues as well as in the adult.

¹ This work was supported in part by a Grant-in-Aid for Research from the Japan Ministry of Education.

² Present address: Fels Research Institute, Temple University School of Medicine, Philadelphia, Pa. 19140.

Received 6/11/73. Accepted 11/ 7/74.