Levels of 2-thiothiazolidine-4-carboxylic acid (TTCA) and effect modification of polymorphisms of glutathione-related genes in vulcanization workers in the southern Sweden rubber industries.
OBJECTIVE
Workers in the rubber industry are exposed to a complex mixture of hazardous substances and have increased risk of developing several diseases. However, there is no up to date survey examining the exposure in the Swedish rubber industry. One of the toxic compounds in the industry is carbon disulfide (CS(2)), which is biotransformed to 2-thiothiazolidine-4-carboxylic acid (TTCA). TTCA is used as a biomarker of CS(2) exposure, but there seem to exist inter- and intraindividual variability; which could partly be due to genetic variation. The aim of the study was to determine TTCA levels and the modifying effects of glutathione-related genes in a group of Swedish rubber workers.


METHODS
Urine was collected from both exposed workers and controls during the last 4 h of the work shift. The level of TTCA in urine was analyzed by liquid chromatograpy tandem mass spectrometry. Genotyping of the single nucleotide polymorphisms GCLC-129, GCLM-588, GSTA1-52, GSTP1-105 and GSTP1-114 and deletions of GSTM1 and GSTT1 were performed with real-time PCR or ordinary PCR and subsequent agarose electrophoresis.


RESULTS
The highest levels of TTCA were found among workers curing with salt bath, hot air, microwaves or fluid-bed, and lower levels were found among workers curing with injection and compression molding. Furthermore, with respect to GSTM1 and GSTT1 there were statistically significant differences in TTCA-levels between genotypes among exposed workers but not among controls. The other five polymorphisms had no impact on the TTCA levels.


CONCLUSIONS
The present study demonstrates relatively high levels of TTCA in urine from Swedish rubber workers. Polymorphisms in GSTM1 and GSTT1 modify the levels.
Jönsson
Lena S
LS
Division of Occupational and Environmental Medicine and Psychiatric Epidemiology, University Hospital, 221 85, Lund, Sweden. lena_s.jonsson@med.lu.se
Broberg
Karin
K
Bergendorf
Ulf
U
Axmon
Anna
A
Littorin
Margareta
M
Jönsson
Bo A G
BA
D000328:Adult; D000368:Aged; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D005260:Female; D005838:Genotype; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D005978:Glutathione / Q000235:genetics* / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007221:Industry; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012408:Rubber; D013548:Sweden / Q000453:epidemiology; D053778:Thiazolidines / Q000633:toxicity* / Q000652:urine
D000395:Air Pollutants, Occupational; D053778:Thiazolidines; C031677:2-thioxo-4-thiazolidinecarboxylic acid; D012408:Rubber; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione