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Volume 47, Number 1-2 >
Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats
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) |
URI: | http://hdl.handle.net/2115/2725 |
Appears in Collections: | Japanese Journal of Veterinary Research > Volume 47, Number 1-2
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Submitter: 獣医学部図書室
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