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

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概要

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• 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.

• 北海道大学の論文
• 1999-08-31

著者

• Iwata H

  Laboratory Of Toxicology Department Of Environmental Veterinary Sciences Graduate School Of Veterina

• Iwata Hisato

  北海道大学 獣医研究 環境獣医

• KHLOOD El.

  Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veteri

• MIYOSHI Hiroyuki

  Laboratory of Experimental Animal Science, Graduate School of Veterinary Medicine, Hokkaido Universi

• IWATA Hisato

  Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veteri

• KAZUSAKA Akio

  Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veteri

• KON Yasuhiro

  Laboratory of Experimental Animal Science, Graduate School of Veterinary Medicine, Hokkaido Universi

• ABOU HADID

  Department of Pharmacology and Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zag

• MOUSTAFE El.

  Department of Pharmacology and Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zag

• GHONIM Mervat

  Department of Pharmacology and Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zag

• FUJITA Shoichi

  Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veteri

• Fujita S

  Laboratory Of Toxicology Department Of Environmental Veterinary Sciences Graduate School Of Veterina

• Fujita Shoichi

  北海道大学 獣医研究 環境獣医

• Abou Hadid

  Department Of Pharmacology And Forensic Medicine And Toxicology Faculty Of Veterinary Medicine Zagaz

• Khlood El.

  Laboratory Of Toxicology Department Of Environmental Veterinary Sciences Graduate School Of Veterina

• Kon Yasuhiro

  Laboratory Of Anatomy Department Of Biomedical Sciences Graduate School Of Veterinary Medicine Hokka

• Kon Yasuhiro

  Laboratory Of Experimental Animal Science Graduate School Of Veterinary Medicine Hokkaido University

• Moustafe El.

  Department Of Pharmacology And Forensic Medicine And Toxicology Faculty Of Veterinary Medicine Zagaz

• Ghonim Mervat

  Department Of Pharmacology And Forensic Medicine And Toxicology Faculty Of Veterinary Medicine Zagaz

• Kazusaka Akio

  Laboratory Of Toxicology Department Of Environmental Veterinary Sciences

• Iwata Hisato

  Laboratory Of Toxicology Department Of Environmental Veterinary Sciences Graduate School Of Veterina

• Miyoshi Hiroyuki

  Laboratory Of Experimental Animal Science Graduate School Of Veterinary Medicine Hokkaido University

• Miyoshi Hiroyuki

  Laboratory Of Experimental Animal Science Department Of Disease Control School Of Veterinary Medicin

• Fujita Shoichi

  Laboratory Of Toxicology

• Fujita Shoichi

  Laboratory Of Toxicology Graduate School Of Veterinary Medicine Hokkaido University

• Kazusaka Akio

  Lavoratory Of Toxicology Graduate School Of Veterinary Medicine Hokkaido University

• Kazusaka Akio

  Graduate School Of Vet. Med. Hokkaido Univ.

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