{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:06:09Z","timestamp":1790849169298,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,5,31]],"date-time":"2005-05-31T00:00:00Z","timestamp":1117497600000},"content-version":"vor","delay-in-days":7790,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[1984,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>C57BL\/6N (<jats:italic>Ah<\/jats:italic><jats:sup>b<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>b<\/jats:sup>) mice have a high\u2010affinity <jats:italic>Ah<\/jats:italic> receptor in tissues, whereas AKR\/J and DBA\/2N (<jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup>) mice have a poor\u2010affinity <jats:italic>Ah<\/jats:italic> receptor. The cytochrome P<jats:sub>1<\/jats:sub>\u2010450 induction response (enhanced benzo[a]pyrene metabolism) occurs much more readily in <jats:italic>Ah<\/jats:italic><jats:sup>b<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>b<\/jats:sup> and <jats:italic>Ah<\/jats:italic><jats:sup>b<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup> than in <jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup> mice, at any given dose of the inducer benzo[a]pyrene.<\/jats:p><jats:p>Embryos from the AKR\/J \u00d7 (C57BL\/6N)(AKR\/J)F<jats:sub>1<\/jats:sub> and the reciprocal backcross were studied during benzo[a]pyrene feeding of the pregnant females. Oral benzo[a]pyrene (120 mg\/kg\/day) given to pregnant <jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup> mice between gestational day 2 and 10 produces more intrauterine toxicity and malformations in <jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup> than <jats:italic>Ah<\/jats:italic><jats:sup>b<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup> embryos. This striking allelic difference is not seen in pregnant <jats:italic>Ah<\/jats:italic><jats:sup>b<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup> mice receiving oral benzo[a]pyrene. Pharmacokinetics studies with [<jats:sup>3<\/jats:sup>H]benzo[a]pyrene in the diet and high\u2010performance liquid chromatographic analysis of benzo[a]pyrene metabolism in vitro by the maternal intestine, liver, and ovary and the embryos of control and oral benzo[a]pyrene\u2010treated pregnant females are consistent with \u201cfirst\u2010pass elimination\u201d kinetics and differences in benzo[a]pyrene metabolism by the embryos and\/or placentas versus maternal tissues. In the pregnant <jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup> mouse receiving oral benzo[a]pyrene, little induction of benzo[a]pyrene metabolism occurs in her intestine and liver; this leads to much larger amounts ofbenzo[a]pyrene reaching her embryos, and genetic differences in toxicity and teratogenesis are manifest. In the pregnant <jats:italic>Ah<\/jats:italic><jats:sup>b<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup> mouse receiving oral benzo[a]pyrene, benzo[a]pyrene metabolism is greatly enhanced in her intestine and liver; this leads to less benzo[a]pyrene reaching her embryos, much less intrauterine toxicity and malformations, and no genetic differences are manifest. More toxic metabolites (especially benzo[a]pyrene 1,6\u2010 and 3,6\u2010quinones) are shown to occur in <jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup> embryos than in <jats:italic>Ah<\/jats:italic><jats:sup>b<\/jats:sup>\/<jats:italic>Ah<\/jats:italic><jats:sup>d<\/jats:sup> embryos. In additional studies, no prenatal or neonatal \u201cimprinting\u201d effect in C57BL\/6N mice by 2,3,7,8\u2010tetrachlorodibenzo\u2010<jats:italic>p<\/jats:italic>\u2010dioxin or Aroclor 1254 on benzo[a]pyrene metabolism later in life was detectable.<\/jats:p><jats:p>These genetic differences in intrauterine toxicity and teratogenicity induced by oral benzo[a]pyrene are just opposite those induced by intraperitoneal benzo[a]pyrene (Shum et al., '79; Hoshino et al., '81). The data in the present report emphasize the importance of the <jats:italic>route of administration<\/jats:italic> when the teratogen induces its own metabolism.<\/jats:p>","DOI":"10.1002\/tera.1420290106","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T14:48:43Z","timestamp":1118501323000},"page":"35-47","source":"Crossref","is-referenced-by-count":65,"title":["Importance of the route of administration for genetic differences in benzo[a]pyrene\u2010induced in utero toxicity and teratogenicity"],"prefix":"10.1002","volume":"29","author":[{"given":"Catherine","family":"Legraverend","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Guenthner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Nebert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,5,31]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7233243"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7444453"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"4712","DOI":"10.1016\/S0021-9258(17)40218-3","article-title":"Ontogenetic expression of polycyclic aromatic compound\u2010inducible monooxygenase activities and forms of cytochrome P\u2010450 in the rabbit. 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