The objective of the proposed work is to investigate the role of bacterial colonization/infection in the etiology of gastric and urinary bladder cancer. Studies in human will explore the relationship of bacterial colonization of the stomach and severity of precancerous lesions with the concentration of carcinogens and their precursors in gastric juice as well as with resultant DNA damage in stomach tissue. Total N-nitroso compounds in human gastric juice will be determined by thermal energy analysis and genotoxins, assayed using the SOS chromotest, will be isolated and identified. Studies in vitro and in vivo in rodents with experimentally induced bacterial colonization/infection of the stomach and bladder will explore the mechanism by which bacteria and inflammatory changes produce alkylation and oxidation of Dna. Alkylated DNA bases in tissues will be determined by immunostaining and immunoassays and levels of 8-hydroxydeoxyguanosine, as a measure of oxidative DNA damage, will be detected by HPLC with electrochemical detection. Unknown carcinogen spectrometry. Bacterial enzymes responsible for nitrosation of amine/amides will be characterized. This approach should lead to a better understand of molecular mechanisms by which bacterial colonization/infection is involved in human carcinogenesis. Once markers for DNA damage that are associate with microbial colonization/infection in the stomach and urinary bladder have been identified, they could be exploited in subsequent epidemiological and intervention studies.
