Effects of acute or chronic polychlorinated biphenyl ingestion on maternal metabolic homeostasis and on the manifestations of embryotoxicity caused by cyclophosphamide in mice.
Diets of mice contained Aroclor 1254 (PCBs; 0, 1, 10 or 100 ppm). Some groups ingested PCBs beginning on gestation day (gd) 6 (vaginal plug positive day = gd 0) and continuing throughout pregnancy (acute exposure). Others were put on PCBs 90 days before mating and continued (chronic exposure) until all animals were sacrificed on gd 18. None of the PCBs diets had adverse effects on offspring. Chronic ingestion of 100 ppm reduced the conception rate. All chronic and acute 100 ppm pregnant mice had significantly altered ratios of liver to body weight. The aim of the different pretreatment regimens was to affect to variable degrees metabolism of cyclophosphamide (CPA). Bioactivation in the dam's liver is a prerequisite for embryotoxic effects in mice. Two doses of CPA were selected that caused malformations in 21.6% (10 mg/kg) or 93.4% (16 mg/kg) of the fetuses when injected on gd 11. The interaction (enhancement, no effect, attenuation) between acute or chronic PCBs and CPA could thus be examined. Double stained fetal limbs and their bone lengths were evaluated. The observations were correlated with cytochrome P-450, the levels of which were elevated in all 100 ppm groups. The activities of enzymes coupled to this hemoprotein family were induced in maternal liver in an exposure mode and PCBs concentration-dependent manner. Body burdens of PCBs in dams and fetuses were related to diet levels in acutely, but not in chronically treated animals. Placental transfer of radioactivity from ring-labelled 14C-CPA, measured in control and 100 ppm chronic mice, was not significantly affected by PCBs.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001140:Aroclors / Q000378:metabolism / Q000633:toxicity*; D001822:Body Burden; D001846:Bone Development / Q000187:drug effects; D020111:Chlorodiphenyl (54% Chlorine); D003520:Cyclophosphamide / Q000378:metabolism / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004347:Drug Interactions; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D013723:Teratogens
D001140:Aroclors; D013723:Teratogens; D020111:Chlorodiphenyl (54% Chlorine); D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls