DNA adduct profiles and levels in placenta, blood and lung in relation to cigarette smoking and smoky coal emissions.
Tobacco smoking and indoor smoky coal combustion emissions lead to exposures to complex environmental mixtures that have been associated with increased lung cancer mortality rates in the USA and Xuan Wei County, China, respectively. Human exposures to benzo[a[pyrene (BaP) present in smoky coal emissions are 20-200 times greater than exposure to BaP from smoking 1-2 packs of cigarettes per day. We compared DNA adducts resulting from cigarette smoking and coal smoke exposures in blood cells, placental syncytial nuclei, whole placental tissue homogenates and lung cells. Postlabelling analysis of DNA isolated from placental tissue of smokers revealed multiple adducts as a diagonal radioactive zone. DNA adduct levels for both white blood cells (WBC) and lymphocyte DNA were approximately 2.5-fold higher in smokers than in non-smokers. One smoking-related adduct was detected in both WBC and lymphocyte DNA, but no exposure-related adducts were detected in either WBC DNA or placental tissue DNA isolated from coal smoke-exposed individuals, despite higher exposure to BaP and aromatic organics. In contrast, discrete adducts unrelated to smoking status were detected, by 32P-postlabelling analysis, in DNA from syncytial nuclei isolated from placental villus samples from smokers and non-smokers. One major placental syncytial adduct co-migrated with a major BaP-derived DNA adduct. DNA adduct levels were approximately four-fold higher in bronchoalveolar lavage (BAL) cells from coal smoke-exposed individuals compared to unexposed individuals and suggest that DNA-reactive intermediates concentrate in the respiratory tract and may not be detectable in whole WBC or placental tissue homogenates. Our findings also suggest that the distribution and concentration of placental DNA adducts may be dependent on the site at which the placenta is sampled.
Gallagher
J
J
US Environmental Protection Agency MD, Genetic Toxicology Division, Research Triangle Park, NC 27711.
Mumford
J
J
Li
X
X
Shank
T
T
Manchester
D
D
Lewtas
J
J
D000293:Adolescent; D000328:Adult; D003031:Coal / Q000009:adverse effects*; D004247:DNA / Q000032:analysis* / Q000097:blood; D004249:DNA Damage; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008297:Male; D010761:Phosphorus Radioisotopes; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000378:metabolism*
D003031:Coal; D010761:Phosphorus Radioisotopes; D012906:Smoke; D004247:DNA