1-(1-glycero)tetradeca-1-3-5-7-9-pentaene and Colonic-Neoplasms

Topics: Cell Division; Colon; Colonic Neoplasms; Diet; Feces; Humans; Lipids; Polyenes

The response of Escherichia coli to genotoxic agents involves the triggering of a complex system of genes known as the SOS response. In E. coli PQ37, a test organism used for the assessment of genotoxicity, lacZ, the beta-galactosidase gene is placed under the control of sfiA, one of the SOS genes through an operon fusion. The induction of beta-galactosidase activity, when the organism is exposed to genotoxic agents, is an indirect measure of the genotoxic activity of the test compound. Incubation of E. coli PQ37 with either 4-nitroquinoline oxide (4-NQO) or one of the fecal mutagens, fecapentaene-12 or -14 (F-12 or F-14) in the presence of sodium taurocholate or sodium deoxycholate resulted in a significant enhancement of induction of beta-galactosidase activity. The molecular mechanisms of 4-NQO-induced mutagenesis in E. coli are similar to those of the effects of UV light in which both replication-dependent and repair-dependent pathways of mutagenesis exist. Since E. coli PQ37 is excision-repair-deficient, alternate pathways are involved in this system. Bile salts by themselves do not trigger the SOS response, and hence their role in enhancing the SOS-inducing potency of mutagens may involve the potentiation of the cleavage-inactivation of lexA (repressor of SOS) by the protein product of the SOS-controlled gene, recA. The potentiating effect of bile salts on the fecal mutagens, F-12 and F-14, has implications in their suspected role in colon carcinogenesis associated with high-fat, low-fiber diets.

Topics: 4-Nitroquinoline-1-oxide; Alkaline Phosphatase; Bile Acids and Salts; Colonic Neoplasms; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Synergism; Escherichia coli; Lithocholic Acid; Mutagens; Polyenes; SOS Response, Genetics; Taurocholic Acid; Ultraviolet Rays

Topics: Bile Acids and Salts; Carcinogens; Cholesterol; Colonic Neoplasms; Diet; Dietary Fats; Feces; Humans; Ketosteroids; Mutagenicity Tests; Mutagens; Polyenes; Structure-Activity Relationship

Topics: Adult; Bacteroides; Carcinogens; Colonic Neoplasms; Feces; Female; Humans; Male; Middle Aged; Mutagens; Polyenes