title: Urinary mutagenicity, CYP1A2 and NAT2 activity in textile industry workers.
abstract: The two major causes of bladder cancer have been recognised to be cigarette smoke and occupational exposure to arylamines. These compounds are present both in tobacco smoke and in the dyes used in textile production. Aromatic amines suffer oxidative metabolism via P450 cytochrome CYP1A2, and detoxification by the polymorphic NAT2. The aim of the present work was to assess the association between occupational-derived exposure to mutagens and CYP1A2 or NAT2 activity. This cross-sectional study included 117 textile workers exposed to dyes and 117 healthy controls. The urinary mutagenicity was determined in 24 h urine using TA98 Salmonella typhimurium strain with microsomal activation S9 (MIS9) or incubation with beta-glucuronidase (MIbeta). Urinary caffeine metabolite ratios: AFMU+1X+1U/17U, and AFMU/AFMU+1X+1U were calculated to assess CYP1A2 and NAT2 activities, respectively. The results show that workers present a strikingly higher urine mutagenicity than controls (p<0.0001), despite the implementation of the new restrictive norms forbidding the industrial use of the most carcinogenic arylamines. Neither NAT2 nor CYP1A2 activity had any effect on the markers of internal exposure to mutagens, since no significant differences were observed when the urinary mutagenicity of slow and fast acetylators (p>0.05) was compared, and the urinary mutagenicity was not significantly associated with the CYP1A2 activity marker (r=0.04 and r=-0.01 for MIS9 and MIbeta, respectively). This study clearly indicates the need for further protective policies to minimise exposure to the lowest feasible limit in order to avoid unnecessary risks.
authors.affiliation: Department of Pharmacology and Physiology, University of Zaragoza, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Fanlo
authors.forename: Blanca
authors.initials: B
authors.lastname: Sinuès
authors.forename: Esteban
authors.initials: E
authors.lastname: Mayayo
authors.forename: Luisa
authors.initials: L
authors.lastname: Bernal
authors.forename: Antonia
authors.initials: A
authors.lastname: Soriano
authors.forename: Begoña
authors.initials: B
authors.lastname: Martínez-Jarreta
authors.forename: Enrique
authors.initials: E
authors.lastname: Martínez-Ballarín
mesh_terms: D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D002110:Caffeine / Q000378:metabolism / Q000652:urine; D003430:Cross-Sectional Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009153:Mutagens / Q000506:poisoning; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D012907:Smoking; D013783:Textile Industry
chemical_list: D009153:Mutagens; D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human