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Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats
Faculty
Veterinary Medicine
Year:
1999
Type of Publication:
Article
Pages:
13-23
Authors:
Iwata, H, Kazusaka, A, Fujita, S, Khlood, EBM, Miyoshi, H, Kon, Y, Abou Hadid, AH, Moustafe, EK, Ghonim, MH
Journal:
JAPANESE JOURNAL OF VETERINARY RESEARCH HOKKAIDO UNIV
Volume:
47
Research Area:
Veterinary Sciences
ISSN
ISI:000082625200002
Keywords :
all-trans-retinoic acid (RA), cytochrome P-450, drug metabolism, fetal malformation, 3-methylcholanthrene (3-MC)
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. Darns 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 similar 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.
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