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

Jpn J Vet Res. 1999 Aug;47(1-2):13-23.

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 approximately 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 severity 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced*
  • Animals
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 Enzyme System / metabolism
  • Female
  • Fetal Resorption / chemically induced
  • Fetus / drug effects*
  • Methylcholanthrene / toxicity*
  • Microsomes, Liver / enzymology
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Teratogens / toxicity*
  • Tretinoin / toxicity*
  • Vitamin A / toxicity*

Substances

  • Teratogens
  • Vitamin A
  • Methylcholanthrene
  • Tretinoin
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP1A1