Relationships among benzo(a)pyrene metabolism, benzo(a)pyrene-diol-epoxide:DNA adduct formation, and sister chromatid exchanges in human lymphocytes from smokers and nonsmokers.
In the present study, benzo(a)pyrene (BP) metabolism, DNA adduct formation, ethoxyresorufin-O-deethylase activity, and sister chromatid exchange induction by BP were compared in human lymphocytes prepared from whole blood of smokers and nonsmokers following an in vitro incubation with BP. There was an approximate 7- to 10-fold variation in all parameters measured. To determine the source of this variation, participants were resampled, the assays were repeated, and all the data were analyzed to assess (a) smoking-related effects, (b) differences in multiple samples from the same individual, and (c) intraindividual, experimental, and interindividual variation. No smoking-related effects were observed except for baseline sister chromatid exchange frequency. The variation observed for BP-related DNA adducts and ethoxyresorufin-O-deethylase activity was primarily due to interindividual variation. For example, in vitro formation of DNA adducts did not change when samples were obtained at different times from the same individual and were not influenced significantly by culture conditions. No significant correlation existed between DNA adduct formation and BP metabolism [correlation coefficient (r) = 0.27] for either the total population or when segregated based on smoking status. Furthermore, no correlation was seen between DNA adducts and sister chromatid exchange induction by BP. Our studies have compared a number of commonly used lymphocyte markers and conclude that it is difficult to predict changes in one marker based on changes in another. However, in vitro formation, of PB-derived DNA adducts is consistent over time for individuals.
Thompson
C L
CL
National Institute of Environmental Health Sciences, Laboratory of Biochemical Risk Analysis, Research Triangle Park, North Carolina 27709.
McCoy
Z
Z
Lambert
J M
JM
Andries
M J
MJ
Lucier
G W
GW
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism*; D000328:Adult; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004249:DNA Damage; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism; D012854:Sister Chromatid Exchange; D012907:Smoking / Q000378:metabolism*
D004101:Dihydroxydihydrobenzopyrenes; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1