The induction of SOS function in Escherichia coli K-12/PQ37 by 4-nitroquinoline oxide (4-NQO) and fecapentaenes-12 and-14 is bile salt sensitive: implications for colon carcinogenesis

The response of Escherichia coli to genotoxic agents involves the triggerin g 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-gal actosidase gene is placed under the control of sfiA, one of the SOS genes t hrough 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 e ither 4-nitroquinoline oxide (4-NQO) or one of the fecal mutagens, fecapent aene-12 or -14 (F-12 or F-14) in the presence of sodium taurocholate or sod ium deoxycholate resulted in a significant enhancement of induction of P-ga lactosidase 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 r eplication-dependent and repair-dependent pathways of mutagenesis exist. Si nce E. coli PQ37 is excision-repair-deficient, alternate pathways are invol ved in this system. Bile salts by themselves do not trigger the SOS respons e, and hence their role in enhancing the SOS-inducing potency of mutagens m ay involve the potentiation of the cleavage-inactivation of lexA (repressor of SOS) by the protein product of the SOS-controlled gene, recA. The poten tiating effect of bile salts on the fecal mutagens, F-12 and F-14, has impl ications in their suspected role in colon carcinogenesis associated with hi gh-fat, low-fiber diets. (C) 2000 Elsevier Science B.V. All rights reserved .