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Lookup NU author(s): Dr Ovnair Sepai Adem BEM
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Nitrotoluenes, such as 2-nitrotoluene, 2,4-dinitrotoluene (24DNT), and 26DNT, are carcinogenic in animal experiments. Humans are exposed to such chemicals in the workplace and in the environment. It is therefore important to develop methods to biomonitor people exposed to nitrotoluenes to prevent the potential harmful effects. For the present study, workers exposed to high levels of these chemicals were investigated. The external dose (air levels), the internal dose (urine metabolites), the biologically effective dose [hemoglobin (Hb) adducts and urine mutagenicity], and biological effects (chromosomal aberrations and health effects) were determined. Individual susceptibility was assessed by determining genetic polymorphisms of enzymes assumed to function in nitrotoluene metabolism, namely glutathione S-transferases (GSTM1, GSTT1, GSTP1), N-acetyltransferases (NAT1, NAT2), and sulfotransferases (SULT1A1, SULT1A2). The levels of urinary metabolites did not correlate with the air levels. The urinary mutagenicity levels determined in a subset of workers correlated with the levels of a benzylalcohol metabolite of DNT. The Hb-adducts correlated with the urine metabolites but not with the air levels. The frequency of chromosomal aberrations (gaps included) was increased (P < 0.05) in the exposed workers in comparison with a group of factory controls and correlated with the level of 24DNT Hb-adducts in young subjects (<31 years). The GSTM1-null genotype was significantly more prevalent in the controls than in the exposed group, which probably reflected an elevated susceptibility of the GSTM1-null genotype to adverse health effects of DNT exposure, such as nausea (odds ratio, 8.8; 95% confidence interval, 2.4-32.2). A statistically significant effect was seen for SULT1A2 genotype on a 24DNT Hb-adduct; GSTP1 genotype on a 2,4,6-trinitrotoluene Hb-adduct; and SULT1A1, SULT1A2, NAT1, GSTT1, and GSTP1 genotypes on chromosomal aberrations in the exposed workers. Copyright © 2006 American Association for Cancer Research.
Author(s): Sabbioni G, Jones CR, Sepai O, Hirvonen A, Norppa H, Jarventaus H, Glatt H, Pomplun D, Yan H, Brooks LR, Warren SH, DeMarini DM, Liu Y-Y
Publication type: Article
Publication status: Published
Journal: Cancer Epidemiology Biomarkers and Prevention
Year: 2006
Volume: 15
Issue: 3
Pages: 559-566
ISSN (print): 1055-9965
ISSN (electronic): 1538-7755
Publisher: American Association for Cancer Research
URL: http://dx.doi.org/10.1158/1055-9965.EPI-05-0677
DOI: 10.1158/1055-9965.EPI-05-0677
PubMed id: 16537716
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