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 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.
Nair
P P
PP
Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, USDA, ARS, Beltsville, MD, USA. ppnair@aol.com
Davis
K E
KE
Shami
S
S
Lagerholm
S
S
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D001647:Bile Acids and Salts / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000139:chemically induced; D003840:Deoxycholic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D008095:Lithocholic Acid / Q000494:pharmacology; D009153:Mutagens / Q000633:toxicity*; D011090:Polyenes / Q000633:toxicity; D013014:SOS Response, Genetics / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D013656:Taurocholic Acid / Q000494:pharmacology; D014466:Ultraviolet Rays
D001647:Bile Acids and Salts; D009153:Mutagens; D011090:Polyenes; D003840:Deoxycholic Acid; D015112:4-Nitroquinoline-1-oxide; D013656:Taurocholic Acid; D008095:Lithocholic Acid; C037358:1-(1-glycero)tetradeca-1,3,5,7,9-pentaene; C037357:1-(1-glycero)dodeca-1,3,5,7,9-pentaene; D000469:Alkaline Phosphatase