Guidong Dai

Terephthalic acid occupational exposure and its effect on organ functions in fiber workers

OBJECTIVES : To investigate the exposure to terephthalic acid (TPA), and to evaluate its effects on organ function including the potential risk factors for uroliths and bladder tumor to TPA. METHODS : Exposure-response modeling was carried out in a cohort of 141 TPA exposure workers and three subgroups were classified according to their urine TPA concentration. The control group consisted of 77 workers with no exposure to TPA dust. The inhalatory exposure of the application workers was estimated from biological monitoring data. Urine and blood samples were collected from all workers before and after work shift to monitor variables of liver, kidney, and lung. Haematological variables and serum biochemistry were valued, pulmonary functions were tested, and ion changes in both serum and urine were measured. RESULTS : Increased urinary excretion of TPA (0-5mmol/molCr after the shift) reflected occupational workers TPA exposure. We also observed the exposure-response relations for the intensity of TPA exposure and the urine variables. Increased serum aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) but within normal range is not increased. The slightly increased serum angiotensin-converting enzyme activity (SACE) was considered to be related to particulate of airborne TPA dust inhalation. No difference between referents and workers exposed to TPA was found for haematological variables. CONCLUSIONS : No clinical organ dysfunctions were found in this investigation working with TPA. However, special precautions are still necessarily taken to avoid excessive or prolonged contact.

Immunohistochemical analysis for cell regulatory proteins in bladder carcinogenesis induced by N-methyl-N-nitrosourea–terephthalic acid

To explore the cell cycle regulatory mechanism in bladder carcinogenesis promoted by terephthalic acid calculi (TPA-calculi), male Wistar rats were initiated with N-methyl-N-nitrosourea (MNU) (20mg/kg b.w. i.p.) twice a week for 4 weeks, and then given basal diet containing 5% TPA, 5% TPA plus 4% Sodium bicarbonate (NaHCO(3)) or 1% TPA for the next 22 weeks. Major regulatory proteins in G1 cell cycle checkpoint including p16(INK4a), cyclin-dependent kinase 4 (Cdk4), cyclin D(1), retinoblastoma protein (pRb) were determined during various stages of urinary bladder carcinogenesis by using immunohistochemistry. In MNU-5% TPA treated group, the incidences of overexpression of Cdk4, cyclin D(1) and pRb in papilloma were significantly higher than these in simple hyperplasia (p=0.023, p<0.001 and 0.001, respectively) and in PN hyperplasia (p=0.042, 0.012 and 0.002, respectively). The incidence of absent expression of p16(INK4a) in papilloma was much higher than that in simple hyperplasia (p=0.004) and in PN hyperplasia (p=0.02). Our results clearly reveal that the deregulation of p16(INK4a)-cyclin D(1)/Cdk4-pRb pathway is associated with bladder carcinogenesis promoted by TPA-calculi.