Effect of 20-Methylcholanthrene on Mouse Embryos

Savkur, Lalita D.; Batra, B. K.; Sridharan, B. N.; Sanghvi, L. D.

doi:10.1530/jrf.0.0030422

Cited by 7 publications

(3 citation statements)

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“…Pregnant mice or rats treated during early or middle gestation with benzola]pyrene, 3-methylcholanthrene, or 7,12-dimethylbenzo[a]anthracene show large increases in embryo lethality and resorption; surviving fetuses have a greater incidence of malformation (1)(2)(3)(4)(5) (9). The Ah locus is responsible for numerous effects, including drug toxicity, DNA binding of reactive intermediates, teratogenesis, and chemical mutagenesis and carcinogenesis (8).…”

mentioning

confidence: 99%

Cultured mouse embryos metabolize benzo[a]pyrene during early gestation: genetic differences detectable by sister chromatid exchange.

Galloway¹,

Perry²,

Meneses³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

107

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Health, Bethesda, Maryland 20205 Communicated by Clement L. Markert, March 10, 1980 ABSTRACT Mouse embryos explanted at 71/2 or 81/2 days of gestation were cultured in medium containing benzo[alpyrene and supplemented with 5-bromodeoxyuridine to allow detection of sister chromatid exchanges. The murine Ah locus regulates the inducible metabolism of polycyclic hydrocarbons such as benzo a pyrene. A high frequency of sister chromatid exchange was induced by benzo[alpyrene in embryos from three Ah-"responsive" inbred strains (BALB/cDub, C3H/AnfCum, and C57BL/6N); there was little or no increase in two Ah-"nonresponsive" inbred strains (AKR/J and DBA/2J). Benzofalpyrene also induced sister chromatid exchanges in the An-responsive recombinant inbred line B6NXAKN-12 but not in the Ah-nonresponsive recombinant inbred line B6NXAKN-3. Sister chromatid exchange in cultured Ah-responsive mouse embryos was thus shown to be a sensitive assay. These data provide direct evidence that genetically responsive mouse embryos (early postimplantation stage) possess the subcellular processes necessary for induction of enzymes that metabolize benzo[alpyrene to its chemically active form(s). Both the Ah regulatory gene product (a cytosolic receptor) and the structural gene product (inducible cytochrome P1450) therefore appear to be functional at an early embryonic age. Furthermore, this metabolic capacity may play an important role in the damage to embryonic cells by po ycyclic hydrocarbons.Polycyclic hydrocarbons have toxic effects on mammalian embryonic development. Pregnant mice or rats treated during early or middle gestation with benzola]pyrene, 3-methylcholanthrene, or 7,12-dimethylbenzo[a]anthracene show large increases in embryo lethality and resorption; surviving fetuses have a greater incidence of malformation (1)(2)(3)(4)(5) (9). The Ah locus is responsible for numerous effects, including drug toxicity, DNA binding of reactive intermediates, teratogenesis, and chemical mutagenesis and carcinogenesis (8).Assessment of the role of the Ah locus in embryo or fetal toxicity requires a demonstration of inducible cytochrome P1-450 activity. The Ah receptor itself can be detected just before birth (10). Cytochrome P1-450 induction in fetal mouse liver can be measured about 18 days or later in gestation; induced aryl hydrocarbon (benzo[a]pyrene) hydroxylase (RH, reduced flavoprotein:oxygen oxidoreductase (RH-hydroxylating), EC 1.14.14.11 activity is detectable in fetal tissues as early as 12-14 days of gestation when pregnant mothers are injected intraperitoneally with polycyclic hydrocarbons (10, 11). The influence of the fetal Ah genotype on the embryotoxicity and teratogenicity of polycyclic hydrocarbons (4, 5) is indirect evidence for inducible cytochrome P1-450 earlier than day 12 of gestation. When a nonresponsive Ahd/Ahd mother, mated with a responsive male Ahb/Ahd heterozygote, is given a large intraperitoneal dose of benzota]pyrene on day 7 or 10 of gestation, there are more resorptions, stillbirths, and congenital anom...

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mentioning

confidence: 99%

Cultured mouse embryos metabolize benzo[a]pyrene during early gestation: genetic differences detectable by sister chromatid exchange.

Galloway¹,

Perry²,

Meneses³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

107

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“…Electrophilic reactants which are teratogenic and mutagenic are acetylaminofluorene (21), aflatoxin (22), alkyltriazenes (23), aminoazobenzene (24), benzanthracenes (25), benzpyrenes (26), carbon tetrachloride (27,28), cycasin (29), 1,2diethylhydrazine (30), ethionine (31,32), methylcholanthrene (33,34), nitrosourea (35)(36)(37), pyrollizidine alkaloids (38). These cytotoxic agents require metabolism or bioactivation.…”

Section: Uterine Ligationmentioning

confidence: 99%

Chemical-biological reactions common to teratogenesis and mutagenesis

Harbison¹

1978

Environ Health Perspect

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Cytotoxic chemicals have in common the ability to act specifically on cells in cycle. Bacteria are more sensitive in the exponential growth phase than when growing slowly in media. Similar observations have been made on a variety of systems ranging from bacteria, yeast, higher plants and invertebrates to vertebrates including primates. The embryo and fetus are highly susceptible to cytotoxic agents because they have continuous groups of cells in the growth phase. Acutely toxic doses may cause cellular death and result in developmental defects or fetal death. Cytotoxic agents can be grouped as alkylating agents, electrophilic reactants, antimetabolites, intercalating agents, amino acid antagonists, spindle poisons, and an additional group of chemicals which covalently bind to DNA. These cytotoxic groups of chemicals may also be mutagenic by interacting with DNA to produce changes in sequences of nucleotides resulting in heritable defects either in a somatic cell line or in a germinal cell line. The mechanisms of chemical-induced teratogenicity and mutagenicity are similar. This commonality is further discussed in the text.

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“…Jackson & Robson (1958) injected methylcholanthrene in rabbit embryos by intra-amniotic and intra-placental injections and observed interruption of pregnancy. In our laboratory, methylcholanthrene was injected in the amniotic fluid of mouse embryos of the strain Swiss Albino and certain striking abnormalities were noticed in the young born, as well as in the subse¬ quent litters born to the mother (Savkur, Batra & Sridharan, 1960).…”

Section: Introductionmentioning

confidence: 99%

Effect of 20-Methylcholanthrene on Mouse Embryos. Ii. Strain C3h (Jax)

Savkur¹,

Batra²,

Sridharan³

1961

Reproduction

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Injection of a microquantity of 20-methylcholanthrene has been made into the fluids of 10-day-old embryos of mice of the C3H (Jax) strain. The treatment resulted in increased prenatal mortality of the embryos and many of the surviving young also showed morphological abnormalities. Examination of the young at weaning age revealed certain deformities and pathological conditions. The relation of some of the abnormalities to naturally occurring mutations is significant. An additional observation was the occurrence of similar abnormalities in the litters born after the treated litter.Since the abnormalities in the present study resemble the ones observed in a similar investigation conducted earlier, as well as the ones caused by irradiation and other teratogenic agents, it is proposed that the mode of action of the carcinogen might also be the same.

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Effect of 20-Methylcholanthrene on Mouse Embryos

Cited by 7 publications

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Cultured mouse embryos metabolize benzo[a]pyrene during early gestation: genetic differences detectable by sister chromatid exchange.

Cultured mouse embryos metabolize benzo[a]pyrene during early gestation: genetic differences detectable by sister chromatid exchange.

Chemical-biological reactions common to teratogenesis and mutagenesis

Effect of 20-Methylcholanthrene on Mouse Embryos. Ii. Strain C3h (Jax)

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