The relationship between urinary metabolites and DNA damage in the urinary bladder epithelium of male and female rats was tested by alkaline elution assay after an
intravesical injection of
OPP or its urinary metabolites. 2-Phenyl-1,4-benzoquinone (PBQ) revealed a weak
DNA-damaging activity in both sexes at 0.05-0.1%.
OPP and
phenylhydroquinone (PHQ) had no effects at the same level. Histopathologically, a single
intravesical injection of 0.1% PBQ induced epithelial
hyperplasia of the bladder epithelium on day 5, but PHQ and
OPP did not induce it. Feeding studies with
OPP-Na were also performed to examine the correlation between urinary PBQ levels and DNA damage in bladder epithelium. Slight DNA damage was observed in males given 1.0 and 2.0%
OPP-Na in the diet for 3-5 months. The damage was dependent upon the dietary levels of
OPP-Na. The amounts of
OPP, PHQ and PBQ in urine were well correlated with the dietary levels of
OPP-Na for male rats. The amounts of
OPP, PHQ and PBQ were greater in male rats than in females given 2.0%
OPP-Na diet for 5 months. The urinary pH of males was slightly higher than that of females. Since 0.4%
sodium bicarbonate did not cause DNA damage in the in-situ study, the urinary alkalinity may not affect the initiation steps of urinary
carcinogenesis by
OPP-Na. The present results indicate that the metabolite PBQ is the reactive species for the initiation steps of
bladder tumors induced by
OPP-Na and
OPP.