Dietary
carcinogens, such
as 2-amino-1-methyl-6-phenylimidazo[4,5-
b]pyridine (
PhIP), and chronic
inflammation have each been implicated as etiologic agents in
prostate cancer. We hypothesized that bacterial
prostatitis would accelerate
PhIP-induced preinvasive lesions in the rat prostate. Male Fischer 344 rats were assigned into 4 groups: Control (untreated),
PhIP (200 ppm in the diet for 20 weeks), Escherichia coli (E. coli, prostatic inoculation in week 10), or
PhIP + E. coli. Study animals were monitored for a total of 52 weeks and were euthanized as necessary based on strict criteria for health status and
tumor burden. Animals treated with E. coli initially developed acute and chronic
inflammation in all lobes of the prostate, whereas
inflammation was observed predominantly in the ventral lobe at time of death.
PhIP + E. coli-treated animals exhibited a marked decrease in survival compared with
PhIP-alone-treated animals as a result of an increase in the number of invasive
cancers that developed at multiple sites, including the skin, small intestine, and Zymbal's gland. Despite their earlier mortality,
PhIP + E. coli-treated animals developed an increased average number of precancerous lesions within the prostate compared with
PhIP-treated animals, with a significantly increased Ki-67 index. Multiplexed serum
cytokine analysis indicated an increase in the level of circulating
IL6 and
IL12 in
PhIP + E. coli-treated animals. Elevated serum
IL6 levels correlated with the development of precancerous lesions within the prostate. These results suggest that
bacterial infections and dietary
carcinogens, two conceivably preventable
cancer risk factors, may synergistically promote
tumorigenesis.