Plasmid pKMIOl

McCann et al. (67) had shown that benzo[a]pyrene was mutagenic for j>. typhimurium only if the bacteria carried the mutation enhancing plasmid pKMIOl whose activity was later shown by Walker (23) to be entirely dependent on bacterial recA and lexA controlled functions. 

Analogues of the umuDC genes can be found in locations other than the bacterial chromosome, for example, plasmid pKMIOl (Walker and Dobson, 1979), a derivative of the drug resistance plasmid R46 (Mortelmans and Stocker, 1979), which carried mucAB genes (Shanabruch and Walker, 1980) (see pp. 879-880). 

Many plasmids are known to possess three properties (1) increased resistance to the bactericidal effects of UV and chemical mutagens, (2) increased spontaneous mutagenesis, and (3) increased susceptibility to UV and chemically induced mutagenesis. Some plasmids possess all three properties others may possess just one, for example, increased susceptibility to mutagenesis (review Mortelmans and Dousman, 1986). Often the profile of activity depends on the DNA repair status of the host cell (Pinney, 1980). Plasmid pKMIOl carries DNA repair genes and has been widely used in strains used in bacterial mutagenicity tests. 

Shanabruch, W.G. and Walker, G.C. (1980). Localization of the plasmid (pKMIOl) gene(s) involved in recA+lexA+-dependent mutagenesis. Mol. Gen. Genet. 129 289-297. 

Walker, G.C. and Dobson, P.P. (1979). Mutagenesis and repair deficiencies of Escherichia coli umu C mutants are suppressed by the plasmid pKMIOl. Proc. Gen. Genet. 172 17-24. 

Aside from the expression of histidine mutations that are easily detected, other properties have been built into the Salmonella strains by mutation to increase their sensitivity. The strains cure defective in DNA excision repair (uvrB). In this case, the increased sensitivity probably is due to the failure to remove some DNA adducts that could lead to mutation. The strains also possess a mutation (rfa) that removes part of the lipopolysaccharide barrier of the bacterial cell wall and thereby makes the cells more permeable to some chemicals. Finally, Salmonella strains TA98 and TA100 contain the R-factor plasmid pkMIOl,277 which increases sensitivity probably by increasing the activity of an error-prone DNA-repair system. 

The presence of mutator plasmids. Excision-deficient strains containing pKMIOl have a higher spontaneous mutation rate at both base substitution and frameshift loci than excision-proficient strains. 

Although not as frequently, several strains of Escherichia coli also are used in genotoxicity testing. E. coli WP2 and its derivatives possess a base-pair substitution in a tryptophan gene.144 Reversion to tryptophan independence can be caused by base-pair substitution mutagens and even some frameshift mutagens. DNA-repair mutations and the pkMIOl plasmid have been introduced into WP2 strains to increase sensitivity. 

---