The use of 4-aminobiphenyl hemoglobin adducts and aromatic DNA adducts in lymphocytes of smokers as biomarkers of exposure.
Two biomarkers of exposure to cigarette smoke, 4-aminobiphenyl-hemoglobin (Hb) adducts and aromatic DNA adducts in lymphocytes, were determined from a population of 55 smokers and 4 nonsmokers. The levels of these adducts were related to daily cigarette consumption and also to (calculated) tar and nicotine intake. The Hb adduct levels seemed to correspond best to the number of cigarettes (cig) smoked, but at a cigarette consumption of >30 cig/day, a saturation effect was observed. Lymphocytic DNA adducts also correlated well with cigarette and tar consumption; for this type of adduct, a saturation level was reached at a dose of approximately 15-20 cig/day. From a subpopulation, a second sample was obtained after 2 months, and the adduct levels were compared with their initial adduct levels. Strong correlations were found between the first and second DNA adduct measurements (r = 0.84). In another subpopulation, resampling was performed after 6 months. No correlation between DNA adduct levels in the first and last samples was found, but 4-aminobiphenyl Hb adduct levels were strongly correlated (r = 0.78), the absolute quantities measured being comparable (paired t test: t = -1.27, P = 0.22, n = 15). We found no influence of GSTM1 and NAT2 polymorphisms on Hb adduct formation and of GSTM1 polymorphism on aromatic DNA adduct formation. A significantly lower aromatic DNA adduct level was observed for intermediate acetylators when compared to slow acetylators.
Dallinga
J W
JW
Department of Health Risk Analysis and Toxicology, Faculty of Health Sciences, Maastricht University, The Netherlands.
Pachen
D M
DM
Wijnhoven
S W
SW
Breedijk
A
A
van 't Veer
L
L
Wigbout
G
G
van Zandwijk
N
N
Maas
L M
LM
van Agen
E
E
Kleinjans
J C
JC
van Schooten
F J
FJ
D000328:Adult; D000611:Aminobiphenyl Compounds / Q000032:analysis* / Q000097:blood; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D018736:DNA Adducts / Q000032:analysis* / Q000097:blood; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D006441:Hemoglobin A / Q000032:analysis*; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012907:Smoking / Q000097:blood*
D000611:Aminobiphenyl Compounds; D015415:Biomarkers; D018736:DNA Adducts; C006757:4-biphenylamine; D006441:Hemoglobin A; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D005982:Glutathione Transferase