Biomarkers of Exposure, Effect, and Susceptibility in Workers Exposed to Nitrotoluenes

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 15; no. 3; pp. 559 - 566
• Main Authors: SABBIONI, Gabriele, JONES, Christopher R, WARREN, Sarah H, DEMARINI, David M, LIU, Yu-Ying, SEPAI, Ovnair, HIRVONEN, An, NORPPA, Hannu, JÄRVENTAUS, Hilkka, GLATT, Hansruedi, POMPLUN, Doreen, HUIFANG YAN, BROOKS, Lance R
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-03-2006
• Subjects: Adult; Air Pollutants, Occupational - adverse effects; Air Pollutants, Occupational - analysis; Air Pollutants, Occupational - chemistry; Biological and medical sciences; Biomarkers - analysis; Biomarkers of human exposure to carcinogens and DNA damaging agents; Carcinogen metabolism; Carcinogenesis, carcinogens and anticarcinogens; Case-Control Studies; Chemical agents; Chemical Industry; Disease Susceptibility - diagnosis; DNA-reactive agents; Environmental carcinogenesis/toxicology; Environmental Monitoring; Epidemiological Monitoring; Female; Follow-Up Studies; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; Hematologic Neoplasms - chemically induced; Hematologic Neoplasms - epidemiology; Hematologic Tests; Hemoglobins - analysis; Humans; Male; Maximum Allowable Concentration; Medical sciences; Middle Aged; Occupational Exposure - adverse effects; Risk Assessment; Sensitivity and Specificity; Toluene; Tumors; Urinalysis; Urinary Bladder Neoplasms - chemically induced; Urinary Bladder Neoplasms - epidemiology; Chromosomal aberration; Sulfotransferases; Genetic variability; Enzyme; Toxicity; Transferases; Genotoxicity; Biological marker; Genotype; Biological indicator; Occupational exposure; Epidemiology; Carcinogen; Cancerology; Glutathione transferase; Dinitrotoluene; DNA; Predisposition; Cytogenetics; Genetics; Occupational medicine; Public health; Polymorphism
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-05-0677

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. (Cancer Epidemiol Biomarkers Prev 2006;15(3):559–66)