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. 1985 May;82(10):3311–3315. doi: 10.1073/pnas.82.10.3311

Cytochrome P-450 metabolic activity in embryonic and extraembryonic tissue lineages of mouse embryos.

R A Pedersen, J Meneses, A Spindle, K Wu, S M Galloway
PMCID: PMC397765  PMID: 3858824

Abstract

Mouse morulae, blastocysts, and embryonic and extraembryonic tissue layers were examined for benzo[a]-pyrene metabolism by cytochrome P-450, using the sister chromatid exchange assay. Benzo[a]pyrene 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[a]pyrene treatment of responsive 7 1/2- and 8 1/2-day (postimplantation-stage) embryos, either intact or as separate tissue layers, increased sister chromatid exchanges in tissues of both embryonic and extraembryonic lineages--i.e., in the embryo proper, in isolated embryonic ectoderm, and in yolk sac, chorion, extraembryonic ectoderm, and extraembryonic endoderm layers. These results indicate that cytochrome P-450 is active in most or all tissues of the early mammalian embryo. It could metabolize xenobiotic molecules reaching the conceptus near the onset of morphogenesis and organogenesis, or it could have another as yet undefined role in normal development.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abe S., Nemoto N., Sasaki M. Comparison of aryl hydrocarbon hydroxylase activity and inducibility of sister-chromatid exchanges by polycyclic aromatic hydrocarbons in mammalian cell lines. Mutat Res. 1983 Oct;122(1):47–51. doi: 10.1016/0165-7992(83)90141-0. [DOI] [PubMed] [Google Scholar]
  2. Allen J. W., El-Nahass E., Sanyal M. K., Dunn R. L., Gladen B., Dixon R. L. Sister-chromatid exchange analyses in rodent maternal, embryonic and extra-embryonic tissues: transplacental and direct mutagen exposures. Mutat Res. 1981 Feb;80(2):297–311. doi: 10.1016/0027-5107(81)90103-2. [DOI] [PubMed] [Google Scholar]
  3. Bennett J., Pedersen R. A. Early mouse embryos exhibit strain variation in radiation-induced sister-chromatid exchange: relationship with DNA repair. Mutat Res. 1984 Apr;126(2):153–157. doi: 10.1016/0027-5107(84)90057-5. [DOI] [PubMed] [Google Scholar]
  4. Binder R. L., Stegeman J. J. Basal levels and induction of hepatic aryl hydrocarbon hydroxylase activity during the embryonic period of development in brook trout. Biochem Pharmacol. 1983 Apr 1;32(7):1324–1327. doi: 10.1016/0006-2952(83)90292-7. [DOI] [PubMed] [Google Scholar]
  5. Clough J. R., Whittingham D. G. Metabolism of [14C]glucose by postimplantation mouse embryos in vitro. J Embryol Exp Morphol. 1983 Apr;74:133–142. [PubMed] [Google Scholar]
  6. Connell J. R. The relationship between sister chromatid exchange, chromosome aberration and gene mutation induction by several reactive polycyclic hydrocarbon metabolites in cultured mammalian cells. Int J Cancer. 1979 Oct 15;24(4):485–489. doi: 10.1002/ijc.2910240417. [DOI] [PubMed] [Google Scholar]
  7. Dziadek M. Modulation of alphafetoprotein synthesis in the early postimplantation mouse embryo. J Embryol Exp Morphol. 1978 Aug;46:135–146. [PubMed] [Google Scholar]
  8. Fantel A. G., Greenaway J. C., Juchau M. R., Shepard T. H. Teratogenic bioactivation of cyclophosphamide in vitro. Life Sci. 1979 Jul 2;25(1):67–72. doi: 10.1016/0024-3205(79)90491-0. [DOI] [PubMed] [Google Scholar]
  9. Filler R., Garner-Shinpock S. Metabolism of benzo(a)pyrene by murine embryonal carcinoma cells. Cancer Res. 1981 Mar;41(3):1104–1109. [PubMed] [Google Scholar]
  10. Filler R., Lew K. J. Developmental onset of mixed-function oxidase activity in preimplantation mouse embryos. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6991–6995. doi: 10.1073/pnas.78.11.6991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Galloway S. M., Perry P. E., Meneses J., Nebert D. W., Pedersen R. A. Cultured mouse embryos metabolize benzo[a]pyrene during early gestation: genetic differences detectable by sister chromatid exchange. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3524–3528. doi: 10.1073/pnas.77.6.3524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gardner R. L. The relationship between cell lineage and differentiation in the early mouse embryo. Results Probl Cell Differ. 1978;9:205–241. doi: 10.1007/978-3-540-35803-9_8. [DOI] [PubMed] [Google Scholar]
  13. Hamilton J. W., Denison M. S., Bloom S. E. Development of basal and induced aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity in the chicken embryo in ovo. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3372–3376. doi: 10.1073/pnas.80.11.3372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lambert G. H., Nebert D. W. Genetically mediated induction of drug-metabolizing enzymes associated with congenital defects in the mouse. Teratology. 1977 Oct;16(2):147–153. doi: 10.1002/tera.1420160206. [DOI] [PubMed] [Google Scholar]
  15. Legraverend C., Guenthner T. M., Nebert D. W. Importance of the route of administration for genetic differences in benzo[a]pyrene-induced in utero toxicity and teratogenicity. Teratology. 1984 Feb;29(1):35–47. doi: 10.1002/tera.1420290106. [DOI] [PubMed] [Google Scholar]
  16. Magnuson T., Epstein C. J. Genetic control of very early mammalian development. Biol Rev Camb Philos Soc. 1981 Aug;56(3):369–408. doi: 10.1111/j.1469-185x.1981.tb00354.x. [DOI] [PubMed] [Google Scholar]
  17. Martin G. R. Teratocarcinomas and mammalian embryogenesis. Science. 1980 Aug 15;209(4458):768–776. doi: 10.1126/science.6250214. [DOI] [PubMed] [Google Scholar]
  18. McLaren A., Bowman P. Genetic effects on the timing of early development in the mouse. J Embryol Exp Morphol. 1973 Oct;30(2):491–498. [PubMed] [Google Scholar]
  19. Nebert D. W., Jensen N. M. The Ah locus: genetic regulation of the metabolism of carcinogens, drugs, and other environmental chemicals by cytochrome P-450-mediated monooxygenases. CRC Crit Rev Biochem. 1979;6(4):401–437. doi: 10.3109/10409237909105427. [DOI] [PubMed] [Google Scholar]
  20. Okey A. B., Bondy G. P., Mason M. E., Kahl G. F., Eisen H. J., Guenthner T. M., Nebert D. W. Regulatory gene product of the Ah locus. Characterization of the cytosolic inducer-receptor complex and evidence for its nuclear translocation. J Biol Chem. 1979 Nov 25;254(22):11636–11648. [PubMed] [Google Scholar]
  21. PIERCE G. B., Jr, MIDGLEY A. R., Jr, RAM J. S., FELDMAN J. D. Pariental yolk sac carcinoma: clue to the histogenesis of Riechert's membrane of the mouse embryo. Am J Pathol. 1962 Nov;41:549–566. [PMC free article] [PubMed] [Google Scholar]
  22. Pal K., Tierney B., Grover P. L., Sims P. Induction of sister-chromatid exchanges in Chinese hamster ovary cells treated in vitro with non-K-region dihydrodiols of 7-methylbenz[a]anthracene and benzo[a]pyrene. Mutat Res. 1978 Jun;50(3):367–375. doi: 10.1016/0027-5107(78)90041-6. [DOI] [PubMed] [Google Scholar]
  23. Poland A., Glover E. 2,3,7,8,-Tetrachlorodibenzo-p-dioxin: segregation of toxocity with the Ah locus. Mol Pharmacol. 1980 Jan;17(1):86–94. [PubMed] [Google Scholar]
  24. Poland A., Glover E., Kende A. S. Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase. J Biol Chem. 1976 Aug 25;251(16):4936–4946. [PubMed] [Google Scholar]
  25. Schreck R. R., Latt S. A. Comparison of benzo(a)pyrene metabolism and sister chromatid exchange induction in mice. Nature. 1980 Nov 27;288(5789):407–408. doi: 10.1038/288407a0. [DOI] [PubMed] [Google Scholar]
  26. Schreck R. R., Paika I. J., Latt S. A. Differences in murine procarcinogen activation enzymes are not accompanied by parallel differences in procarcinogen-induced sister-chromatid exchange. Mutat Res. 1982 May;94(1):143–153. doi: 10.1016/0027-5107(82)90177-4. [DOI] [PubMed] [Google Scholar]
  27. Shire J. G., Whitten W. K. Genetic variation in the timing of first cleavage in mice: effect of maternal genotype. Biol Reprod. 1980 Sep;23(2):369–376. doi: 10.1095/biolreprod23.2.369. [DOI] [PubMed] [Google Scholar]
  28. Shum S., Jensen N. M., Nebert D. W. The murine Ah locus: in utero toxicity and teratogenesis associated with genetic differences in benzo[a]pyrene metabolism. Teratology. 1979 Dec;20(3):365–376. doi: 10.1002/tera.1420200307. [DOI] [PubMed] [Google Scholar]
  29. Spindle A. An improved culture medium for mouse blastocysts. In Vitro. 1980 Aug;16(8):669–674. doi: 10.1007/BF02619196. [DOI] [PubMed] [Google Scholar]
  30. Spindle A. Cell allocation in preimplantation mouse chimeras. J Exp Zool. 1982 Feb 20;219(3):361–367. doi: 10.1002/jez.1402190311. [DOI] [PubMed] [Google Scholar]
  31. Streffer C., van Beuningen D., Molls M., Zamboglou N., Schulz S. Kinetics of cell proliferation in the pre-implanted mouse embryo in vivo and in vitro. Cell Tissue Kinet. 1980 Mar;13(2):135–143. doi: 10.1111/j.1365-2184.1980.tb00456.x. [DOI] [PubMed] [Google Scholar]
  32. Tukey R. H., Nebert D. W. Regulation of mouse cytochrome P3-450 by the Ah receptor. Studies with a P3-450 cDNA clone. Biochemistry. 1984 Dec 4;23(25):6003–6008. doi: 10.1021/bi00320a016. [DOI] [PubMed] [Google Scholar]

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