Effects of 3-methylcholanthrene and phenobarbital on the capacity of embryos to bioactivate teratogens during organogenesis

Juchau, Mont R.; Giachelli, Cecilia M.; Fantel, Alan G.; Greenaway, Jean C.; Shepard, Thomas H.; Faustman-Watts, Elaine M.

doi:10.1016/0041-008x(85)90108-5

Cited by 50 publications

(7 citation statements)

References 20 publications

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“…Cytochrome P-450 activities are present in very low levels in embryos constitutively, but even preimplantation embryos activate BP [ 341. Cytochrome P-448 activity is inducible in day 10 rat and mouse embryos [35-381, although different P-450 activities develop at different stages of development [36,39].…”

Section: Discussionmentioning

confidence: 99%

Micronucleus formation by benzene, cyclophosphamide, benzo(a)pyrene, and benzidine in male, female, pregnant female, and fetal mice

Harper

Ramanujam

Legator

1989

Teratog Carcinog Mutagen

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Male, female, pregnant female, and fetal ICR mice were compared for their acute sensitivity to four single doses of model carcinogens, as measured by micronucleus formation in polychromatic erythrocytes 24 h after treatment in adult bone marrow and fetal liver at days 17-19 of gestation. Cyclophosphamide caused a dose-responsive increase in micronuclei in all groups, without a consistent difference based on gender or pregnancy. At doses of 50 and 75 mg/kg given orally to the pregnant female, the fetuses were three to six times as sensitive as was the mother. Benzo(a)pyrene showed a similarly increased sensitivity of the fetus relative to the other groups, although it is a much weaker clastogen. Benzidine did not cause an increase in micronuclei in any group, although it was thought that the fetal liver might have been sensitive enough to detect it, relative to adult bone marrow. Benzene caused much less response in females than in males and almost no response in pregnant females and their fetuses, even though pregnant females metabolized at least half as much of the total dose as did the males (as measured by the presence of urinary metabolites of benzene). No single metabolite of benzene in the urine was consistently correlated with micronucleus formation in the bone marrow. Several factors must be interacting in different ways for different chemicals to influence their clastogenicity.

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Section: Discussionmentioning

confidence: 99%

Micronucleus formation by benzene, cyclophosphamide, benzo(a)pyrene, and benzidine in male, female, pregnant female, and fetal mice

Harper

Ramanujam

Legator

1989

Teratog Carcinog Mutagen

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“…This result will have important implications for the toxicology of compounds activated by this enzyme. For example, Juchau et al (1985) showed that the incidence of foetal rat malformations elicited by exposure to 2-acetylamino fluorine (AAF) were markedly increased following transplacental induction with MC but not with phenylbarbitone (PB). Furthermore, certain enzymes associated with phase II detoxification such as UDPglucuronosyltransferases do not become functional until after birth (Leakey, 1983).…”

Section: Expression and Inducibility Of P450 Enzymes In Mouse Rat Amentioning

confidence: 99%

Expression and inducibility of P450 enzymes during liver ontogeny

Rich

Boobis

1997

Microsc. Res. Tech.

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“…This has important implications for pharmacological and toxicological studies, particularly of compounds activated by CYP1A2, in the developing rabbit. Transplacental induction by MC, but not by phenobarbital, markedly increases the incidence of fetal malformations caused by 2-acetylaminofluorene, a substrate of CYPlA, in the rat (48).…”

Section: Discussionmentioning

confidence: 99%

Ontogenetic development of the distribution of constitutive and 3-methylcholanthrene-induced CYP1A1 and CYP1A2 in rabbit liver.

Rich

Foster²,

Edwards³

et al. 1993

J Histochem Cytochem.

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We investigated the expression, distribution, and inducibility of 3-methylcholanthrene (MC)-inducible P450 enzymes, CYPlAl and 1A2, in livers of rabbits at different stages of development, ranging from 4 days before birth (-4 days of age) to adulthood. These enzymes were identified by immunoblotting and immunocytochemistry and quantified by dot-blotting, utilizing previously characterized monoclonal antibodies, 107 and 31412, specific for CYPIA2 and both CYPlAl and 1A2, respectively, and a polydonal antibody that recognizes both enzymes. Expression of CYPIA2 is always greater than that of CYPlAl in livers of untreated rabbits, regardless of age. Moreover, immunocytochemistry showed that CYPlAl is evenly distributed throughout the liver at all ages, whereas CYPIA2 is highly localized to only a few scattered cells at 1 day before birth. More hepatocytes express this enzyme perinatally. By 6 days of age, expression of CYPIA2 is confined to a narrow band of centrilobular ceb, but with increasing age the enzyme is expressed in more hepatocytes until weaning, when all hepatocytes are posi-

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Effects of 3-methylcholanthrene and phenobarbital on the capacity of embryos to bioactivate teratogens during organogenesis

Cited by 50 publications

References 20 publications

Micronucleus formation by benzene, cyclophosphamide, benzo(a)pyrene, and benzidine in male, female, pregnant female, and fetal mice

Micronucleus formation by benzene, cyclophosphamide, benzo(a)pyrene, and benzidine in male, female, pregnant female, and fetal mice

Expression and inducibility of P450 enzymes during liver ontogeny

Ontogenetic development of the distribution of constitutive and 3-methylcholanthrene-induced CYP1A1 and CYP1A2 in rabbit liver.

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