Reference

Effects of 3-methylcholanthrene and phenobarbital on the capacity of embryos to bioactivate teratogens during organogenesis

Effects of 3-methylcholanthrene and phenobarbital on the capacity of embryos to bioactivate teratogens during organogenesis. Juchau, Mont R.; Giachelli, Celilia M.; Fantel, Alan G.; Greenaway, Jean C.; Shepard, Thomas H.; Faustman-Watts, Elaine M. (Sch. Med., Univ. Washington, Seattle, WA 98195, USA). Toxicol. Appl. Pharmacol., 80(1), 137-46 (English) 1985. CODEN: TXAPA9. ISSN: 0041-008X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Pregnant Sprague-Dawley rats were divided into 4 groups and given i.p. injections of 3-methylcholanthrene (MC) [56-49-5] in corn oil, corn oil only, phenobarbital (PB) [50-06-6] in Hank's balanced salt soln. (HBSS), or HBSS only. Maternal animals were killed on Day 10 of gestation, and embryos from each group were explanted in medium contg. cyclophosphamide (CP) [50-18-0], 2-acetylaminofluorene (AAF) [53-96-3] or dimethylsulfoxide vehicle. After a 24-h culture period, embryos from dams treated with HBSS, corn oil, or PB/HBSS exhibited no increase in abnormalities (as compared with controls) when either CP or AAF were added to the media. However, embryos transplacentally pre-exposed to MC and subsequently treated during culturing with AFF (but not CP) exhibited striking increases in malformation incidence. Commonly obsd. malformations included abnormally open neural tubes, abnormal flexure rotation, and prosencephalic defects. Homogenates of Day 10 embryos transplacentally preexposed to MC exhibited readily measurable oxidative biotransformation of AAF as assessed with HPLC. Biotransformation of AAF by embryos from the other 3 groups was virtually undetectable. Incorporation of exogenously supplemented bioactivating systems from livers of mature animals indicated that postmitochondrial supernatant fractions (S-9) from male, MC-pretreated rats effectively catalyzed the conversion of AAF (but not CP) to embryotoxic metabolites. Conversely, hepatic S-9 from adult, male, PB-pretreated rats was highly effective in converting CP (but not AAF) to embryotoxic metabolites. The results showed the inducer-specific occurrence of embryonic bioconversion of AAF to embryotoxic metabolites via MC-inducible, P 450-dependent, embryonic enzyme systems.

Effect of 3-methylcholanthrene on the development of aortic lesions in mice

Effect of 3-methylcholanthrene on the development of aortic lesions in mice. Paigen, Beverly; Havens, Mary Bohne; Morrow, Arlene (Med. Cent., Child. Hosp., Oakland, CA 94609, USA). Cancer Res., 45(8), 3850-5 (English) 1985. CODEN: CNREA8. ISSN: 0008-5472. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) The effect of a carcinogen, 3-methylcholanthrene (3-MC)(I) [56-49-5], on the formation and growth of atherosclerotic lesions in mice was examd. Increasing doses of 3-MC (15-1500 mg/kg) increased the no. and size of lipid-staining lesions in the aorta of mice on atherogenic diet for 8 wk. The no. of lesions per mouse was 0.85 for animals treated with 3-MC (150 mg/kg) compared to 0.10 lesions/control mouse (given solvent rather than 3-MC). The progression of lesions over 5-18 wk showed that 3-MC-treated mice also differed from controls in the size of lesions. The total score per mouse at 18 wk of atherogenic diet, based on the no. of lesions and the size of each lesion, indicated by a score of 1 to 4, was 4.31 for 3-MC-treated animals and 2.67 for animals given solvent. The effect of 3-MC treatment could be obsd. during the 1st week on the atherogenic diet. These expts. do not distinguish whether 3-MC affects atherosclerotic lesions by acting as a mutagen or by some other mechanism.