Experimental study on the role of bacteria from urinary tract infections on the bladder carcinogenesis

: The role of bacteria isolated from patients with urinary tract infection (UTI) was studied with a view to the possibility that such bacteria are an etiological factor in the development of bladder cancer. The bacterial strains of Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Serratia marcescens, Staphylococcus epidermidis and Enterococcus faecalis, isolated from patients with UTI at the Kyushu University Hospital, were tested for their nitrate-reducing activity after 1 hr of incubation with sodium nitrate (3.57 mM) in a growth medium (pH 7.2) at 37 degrees C. Of 35 strains tested, 27 strains (77%) showed the ability to reduce nitrate to nitrite with yields ranging from 2 to 310 microM NO2-/hr/10(7) bacterial cells, but in 8 strains (23%) including all the 7 strains of E. faecalis no elevated activity (0.0-0.3 microM) could be detected. Various kinetic profiles were observed for the nitrate-reducing bacteria, at various rate ranging from rapidly to slowly, during 5 hr of incubation. The effect of nitrate-reducing bacteria on mutagen formation in the human urine was examined. The mutagenic activity of smokers' or non-smokers' urine incubated with or without bacteria for 72 hr at 37 degrees C was assayed by the Ames Salmonella/microsome test (using TA100 or TA98 with S9-mix). The mutagenic activity increased in urine incubated with the nitrate-reducing S. marcescens or P. aeruginosa, compared to controls which were incubated without bacteria. Potent mutagenic activity could be induced when the urine concentrate prepared from smokers' urine with an XAD-2 resin column was incubated with sodium nitrite (40 mM) at pH 3 for 4 hrs. The potent mutagenic activity observed here seems to be due to the class of direct-acting mutagen(s), because no metabolic activation was required. The mutagen formation at an optimal pH 4 proceeded rapidly during 4 hrs of incubation, but decreased thereafter. It was noted that even at a physiological pH 6 of human urine, a lower but significant level of mutagenic activity could still be detected. The mutagenic activity of individual urine concentrate from 14 male smokers and from 6 male non-smokers was assayed after 30 min of incubation with or without sodium nitrite (40 mM) at pH 6. Mutagenic activity increased in most of these urine concentrates incubated with sodium nitrite. The levels were variable between individuals with a 1.3- to 53-fold increase compared with the controls incubated without sodium nitrite.(ABSTRACT TRUNCATED AT 400 WORDS)