The ability of bifunctional and monofunctional pyrrole compounds to induced sister-chromatid exchange (SCE) in human lymphocytes and mutations in Salmonella typhimurium

Abstract

The ability to induce sister-chromatid exchange (SCE) in human lymphocytes and mutations in Salmonella typhimurium has been assessed for 4 pyrrole compounds. Three of the compounds, 2,3-bishydroxymethyl-1-methylpyrrole (BHMP), 2-hydroxymethyl-1-methylpyrrole (2HMP) and 3-hydroxy-methyl-1-methylpyrrole (3HMP) are synthetic pyrrolic alcohols; the fourth compound, dehydroretronecine (DHR) is a metabolite of several naturally occuring pyrrolizidine alkaloids. The activity of these compounds was compared with that of mitomycin C (MMC) and decarbamoyl mitomycin C (DCMMC), chemicals related structurally to the pyrrole compounds. All 6 compounds caused an increase in the numbers of SCEs. Whereas the bifunctional pyrroles, DHR and BHMP, and the mitomycins, MMC and DCMMC, increased levels of SCEs by 8–12 times cotrol levels, the monofunctional pyrrols gave increases of only 2 times. Three of the 4 pyrrole compounds (DHR, BHMP and 3HMP) induced mutations in the Salmonella typhimurium based substitution strain TA92, the fourth (2HMP) was not found to be mutagenic in any of the 8 strains used. The mitomycins induced mutations in the frameshift strain TA94 in addition to the base substitution strain TA92, with DCMMC always more mutagenic and less cytotoxic than MMC. All bifunctional compounds induced more mutations and were less cytotoxic in strains containing an efficient excision-repair system. With the pyrrole compounds numbers of SCEs and mutations were only increased when using chemical concentrations significantly higher than those required for the mitomycins: more than twice as high to produce significant numbers of SCEs and more than 100 times as high to produced equal numbers of mutations.