title: Detection of DNA adducts in developing CD4+ CD8+ thymocytes and splenocytes following in utero exposure to benzo[a]pyrene.
abstract: Environmental carcinogen exposure may play an important role in the incidence of cancer in children. In addition to environmental pollutants, maternal smoking during pregnancy may be a contributing factor. Major carcinogenic components of cigarette smoke and other combustion by-products in the environment include polycyclic aromatic hydrocarbons (PAH). Mouse offspring exposed during midpregnancy to the PAH, benzo[a]pyrene (B[a]P), show significant deficiencies in their immune functions, observed in late gestation which persist for at least 18 months. Tumor incidences in these progeny are 8 to 10-fold higher than in controls. We have demonstrated a significant reduction in thymocytes (CD4+ CD8+, CD4+ CD8+ Vbeta8+, CD4+ CD8+ Vgamma2+) from newborn and splenocytes (CD4+ CD8+) from 1-week-old mouse progeny exposed to B[a]P in utero. To investigate possible causes of the observed T cell reduction, we analyzed the thymocytes and splenocytes from progeny and maternal tissues for the presence of B[a]P-DNA adducts. Adducts were detected in maternal, placental and offspring lymphoid tissues at day 19 of gestation, at birth and 1-wk after birth. The presence of B[a]P-DNA adducts in immature T cells may, in part, explain the previously observed T cell immunosuppression and tumor susceptibility in mice exposed to B[a]P in utero. The effects of DNA lesions on progeny T cells may include interference with normal T-cell development. These results provide a possible explanation for the relationship between maternal smoking during pregnancy and childhood carcinogenesis.
authors.affiliation: Dept. of Microbiology and Immunology, Universidad Central del Caribe, Bayamon, PR 00960, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Rodriguez
authors.forename: M J
authors.initials: MJ
authors.lastname: Kohan
authors.forename: L C
authors.initials: LC
authors.lastname: King
authors.forename: W G
authors.initials: WG
authors.lastname: Kirlin
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis*; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D018736:DNA Adducts / Q000032:analysis*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000139:chemically induced; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D002274:Carcinogens, Environmental; D018736:DNA Adducts; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide