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Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats

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Title: Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats
Authors: KHLOOD, El. Bohi M. Browse this author
MIYOSHI, Hiroyuki Browse this author
IWATA, Hisato Browse this author
KAZUSAKA, Akio Browse this author
KON, Yasuhiro Browse this author
ABOU HADID, ALi H. Browse this author
MOUSTAFE, El. Kelish Browse this author
GHONIM, Mervat H. Browse this author
FUJITA, Shoichi Browse this author
Keywords: All-trans-retinoic acid (RA)
Cytochrome P-450.
Drug metabolism.
Fetal malformation.
3-Methylcholanthrene (3-MC)
Issue Date: 31-Aug-1999
Publisher: The Graduate School of Veterinary Medicine
Journal Title: Japanese Journal of Veterinary Research
Volume: 47
Issue: 1-2
Start Page: 13
End Page: 23
Abstract: To investigate the effect of the environmental pollutants, polycyclic aromatic hydrocarbons (PAHs), on retinoic acid-induced teratogenesis, all-trans-retinoic acid (RA) dissolved in corn oil (120 mg/kg) was administered orally to pregnant rats at the 11th day of gestation with and without the prior intraperitoneal treatment with 10 mg/kg 3-methylcholanthrene (3-MC) for 3 days. Dams were killed on the 20th day of pregnancy. The examinations of fetuses revealed that 3-MC barely enough to cause induction of P-450 in pregnant dams had profound embryo-toxic effects : the fetal resorption amounted to~60% of total number of implantations. The fetuses survived weighed less than the control fetuses. All of RA-treated mothers had fetuses with abnormalities, and the main malformations were absence of tail (100%), caudal and sacral malformations (100%), and cleft palate (42%). Pregnant dams received both 3-MC and RA had a reduced severeness of tail anomaly (33%), while the rest, 67%, had short vestigial tail. Caudal and sacral malformations were detected but at a milder degree. We did not observe cleft palate in this group. The concurrent treatment of dams with 3-MC and RA led to an increased inducibility of cytochrome P-450 and subsequently, CYP1A1 dependent enzyme activity higher than those observed after the injection of 3-MC alone. UDP-glucuronyl-transferase activity was also markedly induced in concurrent 3-MC and RA group higher than that in 3-MC alone. We suggest that the induction of P-450 and alteration of metabolic enzyme activities may play an important role in reducing the teratogenic potency of RA. However, RA-treatment did not retard the embryo-toxic effect of 3-MC but rather potentiated.
Type: bulletin (article)
Appears in Collections:Japanese Journal of Veterinary Research > Volume 47, Number 1-2

Submitter: 獣医学部図書室

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