Abstract:Mouse morulae, blastocysts, and embryonic and extraembryonic tissue layers were examined for benzo[aJpyrene metabolism by cytochrome P-450, using the sister chromatid exchange assay. Benzo[alpyrene exposure in vitro increased sister chromatid exchanges in blastocysts of all genetically responsive mice examined [BALB/cDub, C3H/AnfCum, and outbred Dub:(ICR) strains] but not blastocysts of the nonresponsive AKR/J strain. Benzo[alpyrene treatment of responsive 71/2-and 81/2-day (postimplantation-stage) embryos, ei… Show more
“…le). These results confirm experiments involving mouse embryo cultures with benzo(a)pyrene in the growth medium (21). This finding is perhaps not so surprising, since a diffusiontransport system between the developing embryonic circulatory system and maternal blood is initiated prior to day 9 of gestation.…”
Section: Resultssupporting
confidence: 85%
“…There have been earlier reports of constitutive and inducible Cyplal enzyme activity and Cyplal-produced sister chromatid exchange in the postimplantation and preimplantation embryo and placenta (19)(20)(21)(22)(23), whereas we find no expression of inducible Cyplal mRNA in the embryo proper until after 10.5 days of gestation. However, several of these earlier studies represent embryos in culture, where the polycyclic hydrocarbon inducer in the growth medium is highly accessible to the developing embryo with placenta.…”
Section: Resultscontrasting
confidence: 57%
“…Acad Sci. USA 86 (1989) .Ni (19)(20)(21)(22)(23). The finding that neither Cyplal nor Cypla2 mRNA is expressed constitutively during development is strong evidence that neither P450I gene plays a necessary role in differentiation.…”
Section: Resultsmentioning
confidence: 99%
“…It has been suggested that this induction system in animals developed during evolution in response to toxic plant metabolites similar in chemical structure to benzoflavones (9). Although these two genes are believed to be within 25 kilobases of one another on mouse chromosome 9 (18) and controlled by the same aromatic hydrocarbon receptor, the two genes exhibit markedly different developmental-specific (19)(20)(21)(22)(23) and tissue-specific (24,25) regulation. Inducible Cyplal enzyme activity is detectable in the placenta of rats or mice receiving polycyclic hydrocarbons and in the human placenta and fetus during the first trimester when the pregnant woman smokes cigarettes (26)(27)(28).…”
mentioning
confidence: 99%
“…The Cyplal enzyme is typically measured by the hydroxylation of benzo(a)pyrene as substrate (29,30). It is possible that a normally occurring intracellular compound resembling benzo(a)pyrene might be the endogenous substrate for the Cyplal enzyme (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30); for example, the chemical structure of benzo(a)pyrene and other polycyclic hydrocarbons is quite similar to that of steroids.…”
“…le). These results confirm experiments involving mouse embryo cultures with benzo(a)pyrene in the growth medium (21). This finding is perhaps not so surprising, since a diffusiontransport system between the developing embryonic circulatory system and maternal blood is initiated prior to day 9 of gestation.…”
Section: Resultssupporting
confidence: 85%
“…There have been earlier reports of constitutive and inducible Cyplal enzyme activity and Cyplal-produced sister chromatid exchange in the postimplantation and preimplantation embryo and placenta (19)(20)(21)(22)(23), whereas we find no expression of inducible Cyplal mRNA in the embryo proper until after 10.5 days of gestation. However, several of these earlier studies represent embryos in culture, where the polycyclic hydrocarbon inducer in the growth medium is highly accessible to the developing embryo with placenta.…”
Section: Resultscontrasting
confidence: 57%
“…Acad Sci. USA 86 (1989) .Ni (19)(20)(21)(22)(23). The finding that neither Cyplal nor Cypla2 mRNA is expressed constitutively during development is strong evidence that neither P450I gene plays a necessary role in differentiation.…”
Section: Resultsmentioning
confidence: 99%
“…It has been suggested that this induction system in animals developed during evolution in response to toxic plant metabolites similar in chemical structure to benzoflavones (9). Although these two genes are believed to be within 25 kilobases of one another on mouse chromosome 9 (18) and controlled by the same aromatic hydrocarbon receptor, the two genes exhibit markedly different developmental-specific (19)(20)(21)(22)(23) and tissue-specific (24,25) regulation. Inducible Cyplal enzyme activity is detectable in the placenta of rats or mice receiving polycyclic hydrocarbons and in the human placenta and fetus during the first trimester when the pregnant woman smokes cigarettes (26)(27)(28).…”
mentioning
confidence: 99%
“…The Cyplal enzyme is typically measured by the hydroxylation of benzo(a)pyrene as substrate (29,30). It is possible that a normally occurring intracellular compound resembling benzo(a)pyrene might be the endogenous substrate for the Cyplal enzyme (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30); for example, the chemical structure of benzo(a)pyrene and other polycyclic hydrocarbons is quite similar to that of steroids.…”
Agrochemicals have been in use since the early days of modern agriculture. They have been well studied and subject to regulation by various federal and state agencies. There is growing concern about the safety of agrochemicals and how exposure may affect reproductive outcome in humans and other species. This article describes toxicity studies that focus on the developmental and reproductive systems of laboratory animals. The endpoints evaluated include infertility, birth defects (structural defects and functional deficits) and adverse effects on male or female reproductive systems. The classes of agrochemicals discussed include herbicides, insecticides, fungicides, rodenticides as well as fumigants and other miscellaneous chemicals used in agriculture. Data typically submitted to regulatory agencies for the purposes of registration are not readily accessible in the open literature and an attempt has been made to present the findings from such studies. Regulatory issues such as testing requirements and approaches to risk assessment of compounds resulting in adverse reproductive outcome are also outlined. Available epidemiological data on the developmental toxicity of occupational and environmental agrochemical exposure are limited in the sense that while a number of studies have some indications of elevated risk for specific compounds, the epidemiological evidence on the whole is unclear.
Mouse blastocysts were treated with caffeine and/or benzo(a)pyrene (BP), and the effects on development and on induction of sister chromatid exchanges (SCEs) were examined. Caffeine interfered with blastocyst development in a dose-related manner. At 4 mM, the highest concentration tested, caffeine interfered with development of blastocysts to all four endpoints: hatching, trophoblast outgrowth, inner cell mass (ICM) growth, and two-layer (primary endoderm and ectoderm) differentiation of ICMs. At 2 mM, caffeine reduced the incidence of both ICM growth and differentiation but did not affect hatching or formation of trophoblast outgrowths. At 1 mM, caffeine interfered only with ICM differentiation. Cell proliferation was least sensitive to caffeine and was reduced at concentrations of greater than or equal to 2 mM. Induction of SCEs was most sensitive to caffeine exposure; an increase in SCE frequency was observed at 0.1 and 0.5 mM. When caffeine was added to cultures with BP (1 microM, a concentration that was not embryotoxic and did not induce SCEs), both embryotoxic effects and SCE frequency were increased. The enhancing effect on SCE induction was particularly marked; as little as 0.1 mM caffeine was sufficient to cause doubling of induced SCE frequencies when added to cultures with BP.
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