Base-pair substitution mutations

The mutagenicity of benzofa]pyrene for bacteria was demonstrated by Ames et al. (60) They found that in the presence of rat liver homogenates benzo[a]pyrene induced both frameshift and base-pair substitution mutations. When the chemistry of benzo[a]pyrene activation had been worked out and the ultimate carcinogenic form identified as a diolepoxide, BPDE (reviewed in 61-62), several investigators (63-66) showed that BPDE was an extremely potent mutagen, also capable of inducing both frameshift and base-pair substitution mutations. 

Bridges, B.A., Woodgate, R., Ruiz-Rubio, M., Sharif, F., Sedgwick, S.G. and Huhschere, U. (1987). Current understanding ofUV-induced base pair substitution mutation inE. coli with particular reference to the DNA polymerase III complex. Mutation Res. 181 219-226. 

E. coli K12 343/113 contains three markers that are detected by reverse mutation reversion to arginine independence, reversion to nicotinic acid independence, and reversion to the ability to ferment galactose.289 The arg site seems to be more sensitive to chemicals that cause base-pair substitution mutation, whereas the gal and nad sites appear to be more sensitive to chemicals that cause frameshift mutation. 

TRANSITION MUTATION A base-pair substitution mutation in which the purine pyrimidine base-pair orientation is preserved, as in adenine thymine -+ guanine cytosine. 

The commonly used strains for S. typhimurium are TA100 and TA1535 (base pair substitution), TA98 and TA1537 (frame shift mutations) and TA102 for cross-link mutations. The preferred strain of E. coli to detect base pair substitution mutations is WP2. 

In contrast to Mutascreen, the AmesII assay utilizes fluctuation analysis for calculation of reversion frequency. Besides the standard Salmonella tester strain TA98, the AmesII assay also includes new strains each designed to revert by only one specific base pair substitution mutation.13 Thus, when mixed, all six base pair substitutions can be represented in one culture. 

In general, sodium selenite and sodium selenate have produced mixed results in bacterial mutagenicity test systems (Table 3M). Sodium selenite induced base-pair substitution mutations using S. typhimurium and was also positive in the transformation assay using Bacillus subtilis (Kramer and Ames 1988 Nakamuro et al. 1976 Noda et al. 1979). However, negative results have also been reported for sodium selenite both in S. typhimurium and the rec assay using B. subtilis (Lofroth and Ames 1978 Noda et al. 

VanderVeen, L.A., Hashim, M.F., Shyr, Y., and Mamett, L.J. (2003) Induction of frameshift and base pair substitution mutations by the major DNA adduct of the endogenous carcinogen malondial-dehyde. Proc. Natl. Acad. Sci. USA, 100, 14247-14252. 

It has been previously suggested that chelation of o Ls Wi on positions n7 and 0 of guanine might labilize the N proton sufficiently to induce mispairing and base pair substitution mutations (9). Such a complex might also be responsible for the destabilization of DNA at low rb which was observed for c is-DDP but not for trans-DDP or [Pt(dien)Cl]Cl. 

In both these cases, the most significant parameter was hydrophobieity. The positive coefficient with the Ehomo descriptor suggests that amines with higher Ehomo values are more easily oxidized. The lack of the indicator variable in QSAR 22 suggests that extended amines are more capable of inducing frame shift mutations TA 98 is specific for frame-shift mutations while TA 100 is specific for base pair substitution mutations. 

Cell extracts of P. shermanii VKM-103 (wild type), P. shermanii KM-82 mutant (superproducer of vitamin B12), P. acnes CCM 322 and propionic add cocci P. coccoides) were tested as possible sources of antimutagens. The first two strains represented classical propionic acid bacteria, and P. acnes represented cutaneous propionibacteria. In the assay for antimutagenic activity S. typhimuhum TA 1535 his mutant) was used as the test organism (base pair substitution mutations tester). 

We have not directly determined the relative frequencies of frameshift mutations and other mutational events in comparison to the base substitution mutations. However, based on the high frequency of nonsense mutations (11%) among all lacl mutants induced by BPDE and because nonsense mutations are monitorable at less than one-fifth of the lacl codons and, even then, only via certain base pair substitutions, we believe that base substitutions account for a major fraction of mutations induced by BPDE. 

In bacterial systems, 1,2-dibromoethane is a direct-acting mutagen and primarily causes mutations of the base-pair substitution type (Barber et al. 1981 McCann et al. 1975 Moriya et al. 1983 ... 

Positive results from the Saccharomyces cerevisiae gene mutation assay indicate that a substance induces point mutations by base pair substitution or frameshift in the genome. Base pair substimtion and frameshift is explained under the in vivo test. 

The positive dose-response results of the mutagen assays are of interest since both strains showed the nitrosated product to be direct-acting mutagens for both TA98 and TA100 strains. Most N-nitroso compounds cause mutations by base-pair substitution only... 

The di-, tri-, and sulfallates were classified as potent mutagens in the Ames assay with TA 100 and TA 1538 (base-pair substitution mutants), with metabolic activation required (1978). More recent in vitro testing (1981) of di- and triallate with S. typhimurium (strains TA1535.-100, and -98) showed dose-related increases without metabolic activation, but greatly enhanced mutagenicities in the presence of Aroclor 1254-induced rat liver S-9 fraction. These tests indicated that both the di- and triallates can induce base pair substitution and frame shift mutations. 

Several researchers used the Ames test with Salmonella typhimurium to assess the mutagenicity of 2,3,7,8-TCDD in prokaryotic organisms. Predominantly negative results were obtained with tester strains G46, TA 1530, TA 1535, TA 100, TA 1950, and TA 1975, revealing base pair substitutions and with strains TA 1531, TA 1532, TA 1534, TA 1538, TA 98, and TA 1978, revealing frame shift mutations (Geiger and Neal 1981 Gilbert et al. 1980 Mortelmans et al. 1984 Toth et al. 1984). 

Point mutation consists of base-pair substitution ... 

Recently, a quite different model has been proposed that accounts for the appearance of many kinds of mutations, including base pair substitutions, additions and deletions, and small chromosomal mutations of the type that would usually be classified as gene mutations. The model accounts for frequent palindromic sequences (more exactly, imperfect palindromes or quasipalindromes) in DNA that can predispose to alternative DNA structures (e.g., clover leaves) that differ from the usual double helix. The alternative or "secondary" structures can then be acted on by any of a variety of DNA-processing enzymes in ways that may ultimately lead to mutations. The details of these processes are only now becoming manifest, but the general model clearly explains many hitherto mysterious mutational phenomena.371... 

Bacteria Mutation Salmonella typhimurium Salmonella/microsome test histidine reversions Point mutations reversion by base-pair substitution or frameshift mutation <3 wk L L L H... 

Mutation Escherichia coli WP2 tryptophan reversions Point mutations (base-pair substitutions) <3 wk L L M M... 

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