Novel short-term tests for environmental carcinogens

An hypothesised role for cGMP in the regulation of bacterial transposition (Wilkins and Swoboda, 1987) was investigated. No effects on transposition, in either of the two existing transposition tester strains, by membrane permeable derivatives of cyclic nucleotides, or other known modifiers of cyclic nucleotide levels in other systems, was observed, with the exception of a large enhancement of transposition frequency (tf) by the mutagen MNNG. Relatively small increases in tf induced by the oxidative mutagens paraquat and mitomycin C, indicated only mild transposogenic effects by oxygen free radicals, in contrast to their known clastogenic activities. Two new transposition assays were developed. The first based on the indirect measurement of TnS transposition into a self-transmissible plasmid in E. coli KI2 strains, gave accurate and easily quantifiable measurements of tf, with the potential of facile adaption to the study of other transposons. This system was used to investigate the effects of recA and dam, dcm mutations, dam. dcm mutants show elevated levels of baseline tf but no change in the sensitivity towards the transposogenic effects of MNNG. recA hosts were hyper sensitive to MNNG toxicity, but not to transposogenicity. The second new system, an assay of Mud 1 (Apf. lac) transposition in strains of .S'. lyphimurium developed for use in the Ames test, showed that mutagenic and transposogenic effects of MNNG are separate. The use of a transposition based assay for mutagenicity/carcinogenicity seems unreasonable. A test for mutagenic and non mutagenic carcinogens based on the induction of inter- and intrachromosomal recombination (Schiestl. 1989) was investigated. The test detected paraquat, mitomycin C and chemical oxidants as recombinogenic. Similarities in dose response profiles of oxidative mutagens and non-mutagenic carcinogens suggest a possible role for free radical species in the carcinogenetic effect of some non-mutagenic carcinogens