The effects of excision repair and the plasmid pKM101 on the induction of his<sup>+</sup>revertants by chemical agents in<i>Salmonella typhimurium</i>

Inman, Margit Ann; Butler, Mary Ann; Connor, Thomas H.; Matney, Thomas S.

doi:10.1002/1520-6866(1990)3:6<491::aid-tcm1770030605>3.0.co;2-3

Cited by 22 publications

(9 citation statements)

References 21 publications

(15 reference statements)

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“…Finally, constitutive expression from plasmids of the DCM-active GST theta 1-1 from rat in the presence of DCM was more toxic and mutagenic to Methylobacterium and S. enterica serovar Typhimurium TA1535 than that of bacterial DCM dehalogenases, despite a lower conversion rate of DCM to formaldehyde by the rat enzyme under the conditions used (18). In addition, formaldehyde requires a proficient nucleotide excision repair machinery to unfold its mutagenic effects (52), but S. enterica serovar Typhimurium TA1535 is excision repair deficient (26). Inability of the polA mutant to cope with intracellular acid production would constitute another possible explanation for the toxicity of GST-mediated DCM conversion.…”

Section: Discussionmentioning

confidence: 99%

DNA Polymerase I Is Essential for Growth of Methylobacterium dichloromethanicum DM4 with Dichloromethane

2000

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Methylobacterium dichloromethanicum DM4 grows with dichloromethane as the unique carbon and energy source by virtue of a single enzyme, dichloromethane dehalogenase-glutathione S-transferase. A mutant of the dichloromethane-degrading strain M. dichloromethanicum DM4, strain DM4-1445, was obtained by mini-Tn5 transposon mutagenesis that was no longer able to grow with dichloromethane. Dichloromethane dehalogenase activity in this mutant was comparable to that of the wild-type strain. The site of mini-Tn5 insertion in this mutant was located in the polA gene encoding DNA polymerase I, an enzyme with a well-known role in DNA repair. DNA polymerase activity was not detected in cell extracts of the polA mutant. Conjugation of a plasmid containing the intact DNA polymerase I gene into the polA mutant restored growth with dichloromethane, indicating that the polA gene defect was responsible for the observed lack of growth of this mutant with dichloromethane. Viability of the DM4-1445 mutant was strongly reduced upon exposure to both UV light and dichloromethane. The polA -lacZ transcriptional fusion resulting from mini-Tn5 insertion was constitutively expressed at high levels and induced about twofold after addition of 10 mM dichloromethane. Taken together, these data indicate that DNA polymerase I is essential for growth of M. dichloromethanicum DM4 with dichloromethane and further suggest an important role of the DNA repair machinery in the degradation of halogenated, DNA-alkylating compounds by bacteria.Dichloromethane (DCM) is an organic solvent produced industrially in large amounts for a wide range of technical applications (Halogen Solvents Industry Alliance [http://www .hsia.org/white_papers/methchlor.htm]). Its low boiling point and high solubility in water make it a frequently encountered environmental contaminant (36,46). The toxicity of DCM to mammals continues to be investigated intensively (9,14,21,40,45), but its causes are not yet fully characterized at the molecular level. Many specialized aerobic methylotrophic bacteria have been isolated from soil and groundwater environments contaminated with DCM for their ability to grow with DCM as the sole source of carbon and energy (49). Such bacteria rely on a single enzyme, DCM dehalogenase, for this purpose. DCM dehalogenase, which can make up to 20% of the soluble protein during bacterial growth with DCM, was purified and shown to catalyze the glutathione-dependent transformation of DCM to formaldehyde, used in both biomass and energy production, and to two molecules of hydrochloric acid (31). The corresponding gene dcmA was cloned (33) from Methylobacterium dichloromethanicum DM4 (15) (formerly Methylobacterium sp. strain DM4), Methylophilus sp. strain DM11 (3), and, more recently, from several other DCM-degrading strains (49, 50). Sequence analysis indicates that DCM dehalogenases belong to the glutathione S-transferase (GST) enzyme family (27,47). DCM dehalogenases were the first bacterial GSTs to be characterized, but it is becoming clear that the genom...

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Section: Discussionmentioning

confidence: 99%

DNA Polymerase I Is Essential for Growth of Methylobacterium dichloromethanicum DM4 with Dichloromethane

2000

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“…The Ames SaZmonelZa/microsome assay [2] usually detects only gene mutations, since the bacterial strains routinely employed are defective in DNA excision repair (uvrl?). By adding repair positive counterpart strains to the test system, it becomes possible not only to determine the effect of excision repair on the formation of gene mutations but also on the removal of DNA lesions that result in lethal mutations [3]. Thus, one can identify (1) drugs that cause gene mutations only in the presence of a functional excision repair (Class l), (2) drugs that effect mutagenesis in either the presence or absence of excision repair (Class 2), and (3) drugs whose premutational DNA lesions are effectively removed by excision repair (Class 3).…”

Section: Introductionmentioning

confidence: 99%

Genotoxic classification of anticancer drugs

Matney

Nguyen

Connor

et al. 1985

Teratog Carcinog Mutagen

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“…In addition to aflatoxin assays by TLC which was a principal method in this study, two samples of rice dusts were solvent extracted as recommended by Preidecker (1979) and tested for mutagenesis by the Ames plate incorporation assay (Ames et al 1975) using the S-9 microsomal fraction for activation. Salmnella typhimurium strain TA 98 was chosen as the bacterial tester in this assay because it is extremely sensitive to metabolites of aflatoxin (Inman 1980). A computer search of Brazoria County mortality data for the period 1964 through 1975 was made to obtain all deaths for G.I.…”

Section: Methodsmentioning

confidence: 99%

AN ASSESSMENT OF AFLATOXIN B₁ IN THE ENVIRONMENT OF A RICE GROWING COMMUNITY AND ASSOCIATED CANCER RISK

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Cech

1984

Journal of Food Safety

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A study to assess possible exposure to carcinogenic metabolites (aflatoxins) from a mold Aspergillus flavus has been conducted in a rice producing area of Brazoria County, Texas. One hundred samples of unmilled rice were analyzed by thin‐layer chromatography (TLC) for the amount of aflatoxin produced by the mold during rice growth and storage. Two well water samples and two rice elevator dust samples were also checked for possible aflatoxin content. The cancer mortality rates (gastrointestinal and urinary tracts cancers) in the rice‐growing and nonrice‐growing areas of the same county were compared. No aflatoxin was detected by TLC methods in rice, rice dusts or water samples. When extracts of rice dusts were checked for mutagenesis by the Ames Salmonella assay as a supplement to the TLC analysis, the results suggested that these dusts might have contained mutagenic material. This observation notwithstanding, we found no evidence that the rice produced in the studied part of the Gulf Coast had a problem of aflatoxin contamination. Also, cancer mortality rates for two major organ systems were not found to differ for rice‐producing and nonrice‐producing areas of rural Brazoria County.

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The effects of excision repair and the plasmid pKM101 on the induction of his⁺revertants by chemical agents inSalmonella typhimurium

Cited by 22 publications

References 21 publications

DNA Polymerase I Is Essential for Growth of Methylobacterium dichloromethanicum DM4 with Dichloromethane

DNA Polymerase I Is Essential for Growth of Methylobacterium dichloromethanicum DM4 with Dichloromethane

Genotoxic classification of anticancer drugs

AN ASSESSMENT OF AFLATOXIN B₁ IN THE ENVIRONMENT OF A RICE GROWING COMMUNITY AND ASSOCIATED CANCER RISK

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The effects of excision repair and the plasmid pKM101 on the induction of his+revertants by chemical agents inSalmonella typhimurium

Cited by 22 publications

References 21 publications

DNA Polymerase I Is Essential for Growth of Methylobacterium dichloromethanicum DM4 with Dichloromethane

DNA Polymerase I Is Essential for Growth of Methylobacterium dichloromethanicum DM4 with Dichloromethane

Genotoxic classification of anticancer drugs

AN ASSESSMENT OF AFLATOXIN B1 IN THE ENVIRONMENT OF A RICE GROWING COMMUNITY AND ASSOCIATED CANCER RISK

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The effects of excision repair and the plasmid pKM101 on the induction of his⁺revertants by chemical agents inSalmonella typhimurium

AN ASSESSMENT OF AFLATOXIN B₁ IN THE ENVIRONMENT OF A RICE GROWING COMMUNITY AND ASSOCIATED CANCER RISK