DETECTION OF DNA ADDUCTS IN DEVELOPING CD4+CD8+ THYMOCYTES AND SPLENOCYTES FOLLOWING IN UTERO EXPOSURE TO BENZO[a]PYRENE

• Published in: Immunopharmacology and immunotoxicology Vol. 24; no. 3; pp. 365 - 381
• Main Authors: Rodriguez, J. W., Kohan, M. J., King, L. C., Kirlin, W. G.
• Format: Journal Article
• Language: English
• Published: Monticello, NY Informa UK Ltd 01.01.2002; Taylor & Francis; Dekker
• Subjects: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - analysis; Animals; Benzo(a)pyrene - toxicity; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens, Environmental - toxicity; CD4 Antigens - analysis; CD8 Antigens - analysis; Chemical agents; DNA Adducts - analysis; Female; Fetus - drug effects; Humans; Immune Tolerance - drug effects; Male; Medical sciences; Mice; Mice, Inbred C3H; Neoplasms - chemically induced; Pregnancy; Smoking - adverse effects; Spleen - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tumors; Second trimester; Intraperitoneal administration; Thymocyte; Toxicity; Rodentia; Genotoxicity; Splenocyte; Polycyclic aromatic compound; Mutagen; In utero; Pregnancy; Carcinogen; Progeny; Vertebrata; Immunosuppression; Mammalia; Mouse; Newborn animal; Animal; DNA; Molecular adduct
• ISSN: 0892-3973; 1532-2513
• DOI: 10.1081/IPH-120014723

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+Vβ8+, CD4+CD8+Vγ2+) 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.