title: Escherichia coli infection of the urinary bladder: induction of tumours in rats receiving nitrosamine precursors and augmentation of bladder carcinogenesis by N-nitrosobutyl (4-hydroxybutyl)amine.
abstract: Experimental introduction of Escherichia coli type 04 into the subserosa of the urinary bladder of female Fischer 344 rats produced chronic bacterial infection in more than 90% of animals. Groups of rats with bacterial infection were given sodium nitrate and either piperazine (Group 1) or dibutylamine (Group 2) in the drinking-water. Control, noninfected animals received nitrate and either piperazine (Group 3) or dibutylamine (Group 4). At 40 weeks, transitional-cell carcinomas of the bladder were detected in 9/30 rats in Group 1 compared to 0/34 in Group 3 (p less than 0.0005), and in 11/34 rats in Group 2 compared to 0/32 in Group 4 (p less than 0.0003). Early changes were examined by scanning and transmission electron microscopy as well as autoradiography. Preneoplastic liver foci were detected in infected groups of animals receiving amine and nitrate, indicating reabsorption of the carcinogen synthesized in situ to induce distant organ transformation. In another experiment, E. coli infection augmented bladder carcinogenesis by N-nitrosobutyl(4-hydroxybutyl)amine (NBHBA), as indicated by earlier appearance of bladder tumours (six weeks compared to nine weeks) and, after 25 weeks, higher incidences of transitional-cell carcinomas (41/46 compared to 39/53, p less than 0.05), squamous metaplasia (43% compared to 9%, p less than 0.0001), glandular metaplasia (26% compared to 13%, p less than 0.05) and muscle invasion (30% compared to 11%, p less than 0.01) in the E. coli-infected group receiving carcinogen compared to the noninfected group receiving carcinogen, respectively. These results indicate that bacterial infection of the urinary bladder may play a major role in bladder carcinogenesis, both by helping in-situ nitrosamine synthesis and by augmenting carcinogenesis by nitrosamines.
authors.affiliation: Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
authors.forename: N A
authors.initials: NA
authors.lastname: Higgy
authors.forename: A K
authors.initials: AK
authors.lastname: Verma
authors.forename: E
authors.initials: E
authors.lastname: Ertürk
authors.forename: T D
authors.initials: TD
authors.lastname: Oberley
authors.forename: A A
authors.initials: AA
authors.lastname: el-Aaser
authors.forename: M M
authors.initials: MM
authors.lastname: el-Merzabani
authors.forename: G T
authors.initials: GT
authors.lastname: Bryan
mesh_terms: D000588:Amines; D000818:Animals; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity*; D003043:Cocarcinogenesis; D003556:Cystitis / Q000150:complications*; D004927:Escherichia coli Infections / Q000150:complications*; D005260:Female; D009566:Nitrates; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000209:etiology
chemical_list: D000588:Amines; D009566:Nitrates; D009602:Nitrosamines; D002085:Butylhydroxybutylnitrosamine