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BIOMARKERS OF EXPOSURE, EFFECT AND SUSCEPTIBILITY IN WORKERS EXPOSED TO NITROTOLUENES
Citation:
SABBIONI, G., C. R. JONES, O. SEPAI, A. HIRVONEN, H. NORPPA, H. JARVENTAUS, H. GLATT, D. POMPLUN, H. YAN, L. R. BROOKS, S. H. WARREN, D. M. DEMARINI, AND Y. LIU. BIOMARKERS OF EXPOSURE, EFFECT AND SUSCEPTIBILITY IN WORKERS EXPOSED TO NITROTOLUENES. CANCER EPIDEMIOLOGY, BIOMARKERS, AND PREVENTION. American Association of Cancer Research, PHILADELPHIA, PA, 15(3):559-566, (2006).
Impact/Purpose:
To develop methods to biomonitor people exposed to nitrotoluenes in order to reduce the potential harmful effects.
Description:
Nitrotoluenes, such as 2-nitrotoluene, 2,4-dinitrotoluene (24DNT), and 2,6-dinitrotoluene (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 in order to reduce 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, urine mutagenicity), early 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 benzyl alcohol 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). The adduct differences between two genotypes A statistically significant effect was seen for SULT1A2 genotype on Hb-adducts and for GSTP1 and GSTT1 genotypes on chromosomal aberrations in the exposed workers.