The bacterial mutagenicity of synthetic all-trans fecapentaene-12 changes when assayed under anaerobic conditions

Fecapentaenes are potent mutagens produced in the anaerobicenvironment of the human colon. The aim of this study was todetermine the effect of anaerobic conditions on the bacterialmutagenicity of all-trans fecapentaene-12, a synthetic fecapen-taene.Fecapentaene-12 was tested aerobkally and anaer-obkaUy at dosesfrom 0.25 to 4 µg/plate in agar-overlay assays with Salmonellatyphimurium TA98 and TA100 and Escherichia coli WP2urnA(pKM101),and 0.01 to 2 µg/ml in fluctuation test with TA100. Inagar-overlay tests, fecapentaene-12 was less mutagenic to theframeshift mutant TA98 under aerobic conditions than under anaerobicconditions (average slopes of 3.8 and 31.6 revertants/µgrespectively). Aerobic assays using TA100 and E.coli WP2uvrA-(pKM101)gave respective slopes of 62.9 and 167.6. Anaerobic assays withthese base-substitution mutants gave negative results underconditions in which positive controls were mutagenic. However,the numbers of spontaneous revertants in these anaerobic assayswere substantially lower than normal. Microtitre fluctuationtests, known to perform equally well under both aerobic andanaerobic conditions, were conducted with TA100 to confirm thatthe activity of fecapentaene-12 as a base-substitution mutagenwas attenuated under anaerobic conditions. Replicate aerobicassays gave an average slope (revertants/well/µg) of 0.41,compared with 0.056 for anaerobic assays—a > 7-folddifference. There was no significant difference in slope betweenaerobic and anaerobic positive controls. Thus, fecapentaene-12may have two distinct modes of action, acting as a base-substitutionmutagen and as a frameshift mutagen. Anaerobic conditions suppressthe base-substitution activity but not the frameshift activity.These findings suggest that reactive but labile compounds suchas fecapentaenes formed in the faecal stream are unreactivein the anaerobic environment of the lumen of the large bowelbut could become reactive if they reached the oxygenated intestinalmucosa where expression of their genotoxicity could initiateneoplasia. ¹To whom correspondence should be addressed