Micronuclei frequency in urothelial cells of bladder cancer patients, as a biomarker of prognosis.

It has been suggested that the frequency of micronuclei (MN) in defoliated urothelial cells could be used as a biomarker for both the potential risk of bladder cancer (BC) and its progression. To prove this we have carried out a large study evaluating the MN frequency in a group of 383 hospital patients submitted to cystoscopy. From them, 77 were negative in their first cystoscopy, and were considered as a reference group; 79 were positive and were classified as patients with tumor; and 227 with previous bladder cancer submitted to follow-up monitoring were negative and classified as BC patients without tumor. Vesical washes were processed and the obtained cells were placed onto microscope slides for further scoring. To minimize scoring misinterpretations, cells were stained with DAPI, and observed in a fluorescence microscope. Results indicated that patients with BC presented higher incidence of MN than controls (18.29 ± 10.04 vs. 14.40 ± 8.49, P = 0.010, respectively). When individuals with BC were classified depending on whether the BC was a primary or a recidivated tumor, those patients with recurrent BC presented a higher frequency of MN than those where BC was detected for the first time (19.22 ± 9.59 vs. 16.60 ± 10.78, respectively); nevertheless, this increase did not reach statistical significance. Finally, a positive and significant correlation was observed between MN frequency and the degree of the tumor (P = 0.038). All this together would confirm the potentiality of the MN frequency in urothelial defoliated cells assay to be used, at least, in the follow-up and surveillance of BC patients. Environ. Mol. Mutagen. 60: 168-173, 2019. © 2018 Wiley Periodicals, Inc.

Genotoxic effects in swimmers exposed to disinfection by-products in indoor swimming pools.

BACKGROUND: Exposure to disinfection by-products (DBPs) in drinking water has been associated with cancer risk. A recent study (Villanueva et al. 2007; Am J Epidemiol 165:148-156) found an increased bladder cancer risk among subjects attending swimming pools relative to those not attending. OBJECTIVES: We evaluated adults who swam in chlorinated pools to determine whether exposure to DBPs in pool water is associated with biomarkers of genotoxicity. METHODS: We collected blood, urine, and exhaled air samples from 49 nonsmoking adult volunteers before and after they swam for 40 min in an indoor chlorinated pool. We estimated associations between the concentrations of four trihalomethanes (THMs) in exhaled breath and changes in micronuclei (MN) and DNA damage (comet assay) in peripheral blood lymphocytes before and 1 hr after swimming; urine mutagenicity (Ames assay) before and 2 hr after swimming; and MN in exfoliated urothelial cells before and 2 weeks after swimming. We also estimated associations and interactions with polymorphisms in genes related to DNA repair or to DBP metabolism. RESULTS: After swimming, the total concentration of the four THMs in exhaled breath was seven times higher than before swimming. The change in the frequency of micronucleated lymphocytes after swimming increased in association with higher exhaled concentrations of the brominated THMs (p = 0.03 for bromodichloromethane, p = 0.05 for chlorodibromomethane, p = 0.01 for bromoform) but not chloroform. Swimming was not associated with DNA damage detectable by the comet assay. Urine mutagenicity increased significantly after swimming, in association with the higher concentration of exhaled bromoform (p = 0.004). We found no significant associations with changes in micronucleated urothelial cells. CONCLUSIONS: Our findings support potential genotoxic effects of exposure to DBPs from swimming pools. The positive health effects gained by swimming could be increased by reducing the potential health risks of pool water.

Micronuclei assessment in the urothelial cells of women using hair dyes and its modulation by genetic polymorphisms.

Increases in the frequency of micronuclei (MN) in exposed cells can be used as a measure of genotoxicity. Hair dyes contain chemicals that are eliminated by urine and could be genotoxic to urothelial cells. To address this question, we evaluated whether hair dye use is associated with an increase in the frequency of MN in urothelial cells, and whether this association is modified by NAT1 (N-acetyltransferase 1), NAT2 (N-acetyltransferase 2) and GSTM1 (glutathione-S-transferase M1) genotypes. We included 92 women participating as controls in a bladder cancer case-control study in Spain. Of those, 72 had adequate number of cells to be included in the MN analysis. There were no significant differences in the mean MN frequency in women using hair dyes in the last month (9.88 MN/1000 cells), in comparison with the MN in unexposed women (9.50 MN/1000 cells). No statistically significant differences in MN frequency were observed by type of hair dye or color of the hair dye. Comparison of subjects in the highest quartile of MN frequency (> or = 12 MN/1000 cells) and those in the lowest quartile (< or = 4 MN/1000 cells) suggested an association between hair dye use and elevated MN frequency (OR 14.2 (95% CI 0.81-247.8; P=0.069)). None of the polymorphisms examined significantly modified association between hair dye use and frequency of MN. Findings of an increased frequency of MN in urothelial cells of hair dye users suggest a possible genotoxic effect of hair dye compounds and need confirmation in larger studies.