Prokaryote Mutagenicity

Ames Test The Ames test, developed by Bruce Ames and his coworkers at the University of California, Berkeley, depends on the ability of mutagenic chemicals to bring about reverse mutations in Salmonella typhimurium strains that have defects in the histidine biosynthesis pathway. These strains will not grow in the absence of histidine but can be caused to mutate back to the wild type, which can synthesize histidine and hence can grow in its absence. The postmitochondrial supernatant (S-9 fraction), obtained from homogenates of livers of rats previously treated with PCBs in order to induce certain cytochrome P450 isoforms, is also included in order to provide the activating enzymes involved in the production of the potent electrophiles often involved in the toxicity of chemicals to animals. 

Bacterial tester strains have been developed that can test for either base-pair (e.g., strain TA-1531) or frameshift (e.g., strains TA-1537, TA-1538) mutations. Other, more sensitive strains such as TA-98 and TA-100 are also used, although they may be less specific with regard to the type of mutation caused. 

Related Tests. Related tests include tests based on reverse mutations, as in the Ames test, as well as tests based on forward mutations. Examples include  

Reverse mutations in Escherichia coli. This test is similar to the Ames test and depends on reversion of tryptophane mutants, which cannot synthesize this amino acid, to the wild type, which can. The S-9 fraction from the liver of induced rats 

Forward mutations in S. typhimurium. One such assay, dependent on the appearance of a mutation conferring resistance to 8-azaguanine in a histidine revertant strain, has been developed and is said to be as sensitive as the reverse-mutation tests 

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Mutagenicity tests are usually carried out in vitro and in vivo, often using both prokaryotic and eukaryotic organisms. A well-known example is the Ames test, which assesses the ability of a drug to induce mutation reversions in E. coli and Salmonella typhimurium. 

Genotoxicity. Hexachloroethane did not exhibit mutagenic activity in vitro in prokaryotic cells (Haworth et al. 1983 Nakamura et al. 1987 Roldan-Arjona et al. 1991 Simmon and Kauhanen 1978 Weeks et al. 

Genotoxic Effects. 1,2-Dibromoethane has been tested extensively to assess its genotoxic potential in prokaryotic, eukaryotic, and mammalian systems. Tables 2-7 and 2-8 present the results of in vivo and in vitro genotoxicity studies, respectively. The results of these studies indicate that 1,2-dibromoethane is a potent mutagen, producing a broad spectrum of mutations in various test systems. 

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). 

The purpose of this work is to review recent research dealing with both the effect of cisplatin on DNA replication and the mutagenic consequences of translesion synthesis of cisplatin-DNA adducts. Our review will cover both studies performed in prokaryotes (or with prokaryotic proteins) and with eukaryotes (or eukaryotic proteins). 

The mutagenic properties of cisplatin have been demonstrated in a variety of prokaryotic and eukaryotic systems. In this paragraph we will focus on data concerning the molecular bases of this mutagenicity, the pattern of mutations induced with regard to the lesions produced, and the biological consequences for the cell. 

Styrene-7,8-oxide (styrene oxide), the major metabolite of the commercially important chemical styrene, was used as a model electrophile. Styrene is widely used in the manufacture of reinforced plastics and occupational exposure occurs mainly through inhalation of the vapor (14.). The metabolite styrene oxide is mutagenic in both prokaryotic (12) and eukaryotic test systems (16.171 and carcinogenic in rodents (18.). The formation of covalent DNA adducts with styrene oxide in vitro has been reported (18), therefore the development of procedures with the potential for the identification and assessment of styrene oxide damage in vivo clearly need to be explored. 

Prokaryotic promoters. Prokaryotic systems are generally used for rapid screening assays. A well established example is the Ames test that was developed with Salmonella in the 1970s (Ames, 1979 McDaniels et al., 1990 Reifferscheid and Heil, 1996) and is still considered as the standard mutagenicity assay. 

Stover, J.S., Chowdhury, G., Zang, H., Guengerich, F.P., and Rizzo, C.J. (2006) Translesion synthesis past the C8- and N2-deoxyguanosine adducts of the dietary mutagen 2-Amino-3-methylimidazo[4,5-jJquinoline in the Narl recognition sequence by prokaryotic DNA polymerases. Chem. Res. Toxicol, 19, 1506-1517. 

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