Cigarette smoking is one of the major risk factors of
bladder cancer in humans. To date, however, there is no experimental evidence for the effects of inhalation exposure to mainstream cigarette
smoke on bladder
carcinogenesis. The purpose of the present study was to evaluate the effect of inhalation of mainstream cigarette
smoke on mouse bladder
carcinogenesis using a cigarette
smoke inhalation exposure system. Six-week-old male C57BL mice were administered 0.025% N-butyl-N-(4-hydroxybutyl)
nitrosamine (BBN) in their
drinking water for 8 weeks and then divided into 2 groups and exposed to 0 or 300 mg/m(3) wet total
particulate matter mainstream cigarette
smoke for 2 h per day, five times per week, for 22 weeks. The incidences of
bladder tumors (
papilloma and urothelial
carcinoma) tended to increase in the cigarette
smoke-exposed group (25.0%) compared with the controls (15.8%), albeit without a statistically significant difference. We also evaluated
mRNA expression levels of
cytochrome P450 (cyp)
enzymes and
proliferating cell nuclear antigen (
PCNA) in the bladder epithelium. Expression of
cyp1a1 was significantly increased in the cigarette
smoke-exposed group. Cigarette
smoke exposure did not have a significant effect on the expression of
cyp1a2, cyp 1b1, cyp 2a4, cyp 2b10,
cyp 2e1, or
PCNA. In conclusion, limited exposure to mainstream cigarette
smoke for 22 weeks, caused a significant increase in
cyp1a1 expression. This increase coupled with the nonsignificant increase in
bladder tumors suggests that a longer period of exposure is required to clarify the effects of cigarette
smoke on bladder
carcinogenesis.