N-Acetyltransferase 2 genotype, exfoliated urothelial cells and benzidine exposure.

Most studies report an association of the slow N-acetyltransferase 2 (NAT2) status with elevated bladder cancer risk. In this study, NAT2 genotypes and the decades-long records of Papanicolaou's grading of exfoliated urothelial cells in a former benzidine-exposed cohort of the Shanghai dyestuff industry (29 bladder cancer patients; 307 non-cancer cohort members, some of them presenting different grades of pre-malignant alterations of exfoliated urothelial cells) were investigated. The cohort members had been enrolled in regular medical surveillance since mid-1980s. No overall increase of slow NAT2 genotypes in the former benzidine-exposed bladder cancer patients was found, compared with non-diseased members of the same cohort. A lower presentation of the homozygous wild genotype NAT2 4/4 was observed in bladder cancer patients, compared with non-diseased members with averaged Papanicolaou's grading (APG)3 II (OR=0.31, 95 percent CI 0.10-0.96, p=0.034) or with APG less than II (OR=0.36,95 percent CI 0.12-1.10, p=0.063). Nevertheless, neither a protective influence of rapid NAT2 genotypes on bladder cancer risk nor on pre-malignant cytological alterations could be confirmed by the present data.

Detection of mutant p53 protein in workers occupationally exposed to benzidine.

To investigate the expression of mutant p53 protein in workers occupationally exposed to benzidine, we detected mutant p53 protein by immuno-PCR assay in the serum of 331 benzidine-exposed healthy workers, while we classified exfoliated urothelial cells in urine samples with Papanicoloau's grading (PG). The Papanicoloau's grading classified exfoliated urothelial cells of the subjects from grade I (normal cells) to grade III (suspicious malignant cells). The subjects were also divided into high, medium and low exposure groups according to the exposure intensity index. The results revealed that mutant p53 protein in the medium and high exposure groups were significantly higher than the in low exposure group (p<0.05), and in PG II and III were significantly higher than in the PG I (p<0.05). There was no significant differences among Papanicoloau's gradings strata in the low exposure group on the incidence and quantity of mutant p53 protein. In the medium and high exposure groups, the incidence and/or quantity of mutant p53 protein in the stratum of PG II and/or III were significantly higher than that of PG I (p<0.05). Detection of mutant p53 protein in conjunction with benzidine exposure level and Papanicoloau's gradings of exfoliated urothelial cells could provide more information to help us elevate surveillance efficiency and diagnose bladder cancer in the early period.

[Expression of protein p53 in workers occupationally exposed to benzidine and bladder cancer patients.].

OBJECTIVE: To study expression of mutant p53 protein in workers occupationally exposed to benzidine and bladder cancer patients. METHODS: Mutant p53 protein in serum from the workers occupationally exposed to benzidine and bladder cancer patients were determined with Immuno-PCR, while exfoliated urothelial cells in the urine samples were classified with Papanicolau grading. RESULTS: Positive rate of mutant p53 protein increased with the exposed intensity index in workers occupationally exposed to benzidine. The positive rate of mutant p53 protein in bladder cancer patients (83.3%) was significantly higher than that in the group 1 of exposed intensity index. The average scanning integrals of PCR amplified band in the group of bladder cancer patients and group 2 of exposed intensity index were both higher than that in the group 1 significantly. Workers in the groups of different exposed intensity indices were further stratified according to Papanicolau grades. In the group 2 of exposed intensity index, the average scanning integrals of PCR amplified band in the stratum of Papanicolau grade II and III were significantly higher than that in the strata of Papanicolau grade I. And in the group 3 of exposed intensity index, the positive rate of mutant p53 protein in the strata of Papanicolau grade III was higher than that in the strata of Papanicolau grade I significantly. CONCLUSION: The increase of exposed intensity may not only result in the positive rate of mutant p53 protein, but also the quantity of mutant p53 protein in serum within the low range of benzidine exposure. Once the exposed intensity was beyond that spectrum, the positive rate of mutant p53 protein in serum and the average scanning integrals of PCR amplified band were no longer enhanced with the increase of exposed intensity. There was tight correlation between Papanicolau grade of exfoliated urothelial cells and the positive rate or the quantity of mutant p53 protein for the higher benzidine exposure intensity.