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PubMed2001

DNA-damaging potential and glutathione depletion of 2-cyclohexene-1-one in mammalian cells, compared to food relevant 2-alkenals.

2-Cyclohexene-1-one (CHX) occurs as a natural ingredient in some tropical fruits and has been detected as a contaminant in certain artificially sweetened soft drinks. To elucidate its cytotoxic/genotoxic effectiveness, CHX was tested in mammalian cell lines (V79 and Caco-2) and in primary human colon cells in comparison to structurally related 2-alkenals. Inhibition of cell growth (IC(50)) and cytotoxicity (LC(50)) were determined by protein staining with sulforhodamin B (SRB) and by trypan blue exclusion, respectively. DNA damage--both strand breaks and oxidised purines--was quantified by comet assay. Depletion of glutathione was measured in a kinetic assay, based on 5-thio-2-nitrobenzoate (TNB) formation. For CHX, a moderate cytotoxicity was observed after 1h incubation in V79 cells (LC(50): 4.75mM). The 2-alkenals ((E)-2-octenal (OCTE), (2E,4Z)-2,4-hexadienal (HEXDI), (E)-2-nonenal (NONE), (2E,6Z)-2,6-nonadienal (NONDI)) exhibited a distinctly higher cytotoxicity, except for (E)-2-hexenal (HEX) (LC(50): 3.67mM) and cinnamaldehyde (CA) (LC(50): 4.45mM). If the incubation time was prolonged to 24h, an IC(50) of 15microM was obtained for CHX which is well within the range obtained for the 2-alkenals (4 and 17microM). Concentration-dependent DNA damage was observed after 1h incubation with CHX. The respective DC(50) values (concentration inducing DNA damage in 50% of cells) were 272microM (V79) and 455microM (Caco-2). All 2-alkenals were more active under these conditions, except for CA. In primary human colon cells, CHX (800microM, 30min) exhibited a weak, but still significant DNA-damaging potential. Glutathione levels in V79 cells were effectively depleted (down to approximately 20%) by CHX concentrations not yet inducing DNA damage (c < or = 50microM). Incubation with CHX or 2-alkenals (50 and 100microM, 1h), followed by H2O2 treatment (5min, 25microM) resulted in increased levels of oxidised purines in the modified comet assay. CHX and HEX, additionally tested in primary human colon cells, depleted glutathione and increased the sensitivity towards oxidative stress.

Aldehydes↗
PubMed2002

The genotoxicity of priority polycyclic aromatic hydrocarbons in complex mixtures.

Risk assessment of complex environmental samples suffers from difficulty in identifying toxic components, inadequacy of available toxicity data, and a paucity of knowledge about the behavior of geno(toxic) substances in complex mixtures. Lack of information about the behavior of toxic substances in complex mixtures is often avoided by assuming that the toxicity of a mixture is simply the sum of the expected effects from each mixture component, i.e. no synergistic or antagonistic interactions. Although this assumption is supported by research investigating non-genotoxic end-points, the literature describing the behavior of genotoxic substances in complex mixtures is sparse and, occasionally, contradictory. In this study, the results of polycyclic aromatic hydrocarbon (PAH) analyses on freshwater bivalves were used to prepare realistic mixtures containing up to 16 PAHs. The SOS genotoxicity of the mixtures and each component were then assessed in an effort to evaluate the additivity of PAH genotoxicity. At nominal PAH concentrations above 1 microg/ml, observed genotoxic responses were far lower than those predicted under the assumption of additivity. At nominal concentrations below 0.75 microg/ml, differences are smaller and occasionally negligible, indicating that the genotoxicity of unsubstituted homocyclic PAHs is additive or slightly less than additive. Other researchers who have investigated the mutagenicity, carcinogenicity, and DNA binding activity of mixtures containing unsubstituted homocyclic PAHs have also reported additive effects. Therefore, the mutagenic risk posed by simple, well-characterized mixtures of priority PAHs can reasonably be estimated as the sum of the risks posed by the mixture components. Current data indicate that less-than-additive effects likely result from saturation of metabolic pathways needed to activate mutagenic PAHs.

Animals↗
PubMed2002

The influence of the solvents DMSO and ethanol on the genotoxicity of alpha,beta-unsaturated aldehydes in the SOS chromotest.

alpha,beta-Unsaturated aldehydes are ubiquitous environmental pollutants, important industrial chemicals, have mani-fold biological functions in plants and insects and are natural products in food. They are endogenously formed in animals and humans during lipid peroxidation and arachidonic acid oxidation and are genotoxic, mutagenic and carcinogenic. Crotonaldehyde and 2-hexenal in food may contribute to general carcinogenicity in humans. The high bacterial toxicity of these compounds leads to problems in genotoxicity testing in bacterial systems. Recently, we have shown that using ethanol as solvent instead of dimethylsulfoxide (DMSO) results in an increase in the induction factors and the SOS-inducing potency of alpha,beta-unsaturated ketones in the SOS chromotest. Here, we demonstrate that utilization of ethanol as solvent also improves the testing of alpha,beta-unsaturated aldehydes. Five aldehydes out of nine tested were clearly positive in the SOS chromotest according to the criteria of Quillardet, i.e. acrolein, crotonaldehyde, 2,4-hexadienal, 2-methylacrolein and 2-ethylacrolein, three further, 2-hexenal, 2-heptenal and 2-propylacrolein showed a dose dependent increase of the induction factors which was however lower than 1.5 times that of the background. Only 2-butylacrolein did not lead to an increase in the induction factors. With DMSO as solvent only the three aldehydes acrolein, crotonaldehyde and 2,4-hexadienal showed an increase in the induction factor, which was however lower than 1.5 that of the background. Utilization of ethanol allows to establish structure genotoxicity relationships for alpha,beta-unsaturated aldehydes in the SOS chromotest. Genotoxicity decreases with increasing degree of substitution. The decreasing genotoxicities can be explained (a) by increasing bacterial toxicity due to increasing lipophilicities of the higher substituted aldehydes and (b) by decreasing reactivity due to steric hindrance by the alkyl substituents.

Aldehydes↗
PubMed2002

Genotoxic activation of benzophenone and its two metabolites by human cytochrome P450s in SOS/umu assay.

The genotoxic potential of benzophenone and its metabolically related compounds, benzhydrol and p-benzoylphenol, was investigated using human cytochrome P450 (P450) enzymes. Benzophenone and its two metabolites (0.1-1mM) showed a suppression of bacterial growth without any P450 system, but no induction of umu gene expression was observed in Salmonella typhimurium TA1535/pSK1002. Human liver microsomes induced the bacterial cytotoxicity of these compounds without any umu gene expression. On the other hand, with the addition of Escherichia coli membranes expressing recombinant human P450 2A6 and NADPH-cytochrome P450 reductase (NPR), benzophenone showed umu gene expression (64 umu units/min/nmol) P450 2A6). Moderate activation of benzophenone by P450 1A1/NPR membranes, 1A2/NPR membranes, or 1B1/NPR membranes was also observed. Activation of benzhydrol and p-benzoylphenol by the P450/NPR system was similar to that of benzophenone. These results suggest that benzophenone and its metabolically related benzhydrol and p-benzoylphenol can be bioactivated by P450 2A6 and P450 family 1 enzymes. Until now, benzophenone has been investigated mainly in terms of estrogenic activity and cytotoxicity, however, the genotoxic activation of benzophenone by human cytochrome P450s should be examined in terms of the risks to humans.

Animals↗
PubMed2002

Genotoxicity of gliotoxin, a secondary metabolite of Aspergillus fumigatus, in a battery of short-term test systems.

The genotoxic effects of gliotoxin, a known fungal secondary metabolite, were studied. Gliotoxin was purified from cultivation medium of Aspergillus fumigatus isolated from the indoor air of a moisture problem house. The genotoxicity of gliotoxin was assessed both in bacterial test systems including bacterial repair assay, Ames Salmonella assay and SOS-chromotest, and in mammalian cells using single cell gel (SCG) electrophoresis assay and sister-chromatid exchange (SCE) test. Gliotoxin was found to be genotoxic in the bacterial repair assay but, not in the Salmonella test or SOS-chromotest. A dose-related increase in DNA damage was observed in mouse RAW264.7 macrophages exposed to gliotoxin for 2h in plain medium in the SCG assay. In contrast to the positive response in the SCG assay, gliotoxin did not induce any clear, dose-related increase in SCEs in Chinese hamster ovary (CHO) cells.

Air Pollution, Indoor↗
PubMed2003

Genotoxic hazards of long-term application of wastewater on agricultural soil.

In the city of Aligarh (India), wastewater coming from both industrial and domestic sources and without any treatment is used to irrigate the agricultural crops. This practice has been polluting the soil, and the pollutants could possibly reach the food chain. For the above reason, soil irrigated with wastewater was sampled and monitored for the presence of genotoxic agents using three biological assays namely Ames Salmonella/mammalian microsome test, survival of SOS defective E. coli K-12 mutants and bacteriophage lambda systems. Extracts from soils were prepared using different organic solvents, i.e. methanol, acetonitrile and acetone. TA98 was found to be most sensitive strain to all the soil extracts. A significant decline in the survival of DNA repair defective E. coli K-12 mutants as compared to their isogenic wild-type counterparts were observed when treated with soil extracts. PolA was found to be the most sensitive strain. A remarkable decline in the plaque forming units was also observed when tested with the soil extracts. Extracts of soil that has been irrigated with ground water were also tested by the above three biological assays to compare the results.

Agriculture↗
PubMed1997

Genotoxicity of platinum and palladium compounds in human and bacterial cells.

Platinum and palladium belong to the group of platinum elements and thus share many chemical properties. Platinum coordination complexes are known to be carcinogenic and genotoxic in mammalian and bacterial cells. However, little is known about palladium genotoxicity. This study compares and evaluates the genotoxic potential of selected platinum and palladium metal salts in mammalian and bacterial cells using the cytokinesis-block micronucleus test (MNT) with human lymphocytes and the bacterial SOS chromotest. Carboplatin, cisplatin(II), transplantin(II), PtCl4(IV), and K2PtCl4(II) caused a significantly elevated genotoxicity in the MNT and the SOS chromotest. The platinum compounds PtCl2(II) and K2PtCl6(IV), and the divalent palladium salts PdCl2(II), K2PdCl4(II), Pd(NH3)2J2(II), Pd(NH3)4Cl2(II), and transpalladium(II) were not genotoxic in the MNT nor in the SOS chromotest. Therefore, evidence for palladium genotoxicity seems to be low in mammalian and bacterial cells.

Adult↗
PubMed1997

Genotoxicity of selected metal compounds in the SOS chromotest.

Knowledge concerning the genotoxicity of inorganic metal compounds in the SOS chromotest is limited. Up to now, only Cr(VI), Sn(II) and the platinum antitumor compound cisplatin(II) were shown to be genotoxic in this test system. However, for Cr(VI) and Sn(II), a positive reaction could only be achieved in cytotoxic dose ranges. The aim of the present study was to provide additional data concerning metal salt genotoxicity in the SOS chromotest. Therefore, 14 metal/metalloid salt compounds of platinum, palladium, rhodium, arsenic, antimony and chromium were tested. Four platinum salts, K2PtCl4, cis-Pt(NH3)2Cl2 (cisplatin), trans-Pt(NH3)2Cl2 (transplatin) and PtCl4 as well as two rhodium compounds tested, K2RhCl5 and (NH4)3RhCl6, could be shown to be genotoxic in the chromotest using the tester strain Escherichia coli PQ37. A moderate genotoxicity was shown by the two Cr(VI) compounds K2CrO4 and K2Cr2O7. All palladium compounds and all the other metal salts tested were unable to induce a significant SOS response.

Alkaline Phosphatase↗
PubMed1997

Genotoxicity of six pesticides by Salmonella mutagenicity test and SOS chromotest.

Two in vitro tests (Ames test and SOS chromotest), one for bacterial mutagenicity and one for primary DNA damage, were assayed to determine the genotoxic activity of 6 pesticides (atrazine, captafol, Captan, chlorpyrifosmethyl, molinate and tetrachlorvinphos). Assays were carried out both in the absence and presence of S9 fractions of liver homogenate from rat (Sprague-Dawley) pretreated with Aroclor 1254. Captan and captafol were genotoxic on both the Ames test and the SOS chromotest. Comparisons with mutagenesis data in Salmonella indicated that the SOS assay detected as genotoxic the pesticides that were mutagenic on the Salmonella test. Non-genotoxic effects were not detected in vitro either in the Salmonella/microsome assay nor in the SOS chromotest when bacterial tester strains were exposed to atrazine, molinate, chlorpyrifosmethyl and tetrachlorvinphos in the absence or presence of S9 mix.

Animals↗
PubMed1997

Detection of genotoxic substances in bivalve molluscs from the Saguenay Fjord (Canada), using the SOS chromotest.

Few studies have employed bioassays to investigate the accumulation of genotoxins in aquatic biota that inhabit areas contaminated with industrial and municipal wastes. This study employed the SOS Chromotest, a short-term bacterial genotoxicity assay, to investigate the presence of genotoxins in bivalve molluscs from the Saguenay Fjord (Canada). Genotoxicity analyses were performed on dichloromethane extracts of Mya arenaria and Mytilus edulis collected downstream from several aluminum refineries and forestry products industries known to produce and release genotoxic substances. The results confirmed that bivalve molluscs inhabiting downstream regions are contaminated with both direct-acting and pro-genotoxic substances. In several cases, SOS response induction factors exceeded 3.0. The results failed to reveal a clear downstream trend of decreasing genotoxicity with increasing distance from the presumed industrial sources(s). A significant relationship (r2 = 0.61, p < 0.007) between a demographic variable (population near shoreline) and lipid-corrected genotoxic potency suggest that the accumulated direct-acting genotoxins may be of municipal origin. Significant relationships between tissue extract genotoxicity (r2 = 0.75, p < 0.003) and tissue PAH contamination (r2 = 0.77, p < 0.0001) and drainage basin area suggests that the bivalves are accumulating airborne contaminants deposited on the surface of the relevant drainage basins. In spite of contamination with genotoxic PAHs, the addition of rat liver microsomal enzymes reduced the genotoxic potency of all samples investigated (31-94% decrease). The results also revealed a significant relationship between tissue extract genotoxicity and PAH concentration (r2 = 0.72, p < 0.0005). Further analyses confirmed that a variable portion (7-97%) of the S9-activated tissue extract genotoxicity can be attributed to the detected PAHs. Although the sources, identity and effects of genotoxins accumulated by bivalves of the Saguenay Fjord remain to be determined, the study has confirmed the utility of the SOS Chromotest in environmental monitoring of aquatic biota.

Animals↗
PubMed1997

Increase of sensitivity and validity of the SOS/umu-test after replacement of the beta-galactosidase reporter gene with luciferase.

The SOS/umu-test with Salmonella typhimurium TA1535/pSK1002 as tester strain is a rapid and valuable bacterial assay for screening of umuC-dependent mutagenic potential of chemical compounds and chemicals relevant to environmental pollution. The initial assay was modified by replacing the beta-galactosidase reporter gene with luciferase. Thereby, the sensitivity of the umu-test was increased significantly and the susceptibility to intensively coloured solutions was reduced. The alternative enzyme assay in the modified umu-test (umu-Luc) represents an independent method which allows to confirm the colorimetric results obtained with the original SOS/umu-test system (umu-Gal) by measuring the beta-galactosidase activity. It has been proved that for several genotoxins an increased induction rate could be achieved by applying the new umu-Luc test.

Blotting, Western↗
PubMed1998

New Escherichia coli WP2 tester strains highly sensitive to reversion by oxidative mutagens.

New Escherichia coli strains have been added to the WP2 mutagenicity test for the specific detection of oxidative mutagens. Strain IC203 derives from WP2 uvrA/pKM101 and is highly sensitive to oxidative stress due to a deficiency in the OxyR function. Following exposure to t-butyl hydroperoxide (BuOOH) or menadione (MD), but not to 4-nitroquinoline 1-oxide (4NQO), strain IC203 (oxyR) shows increased mutability with respect to the oxyR+ parent. The advantage that the OxyR deficiency confers on IC203 strain in detecting oxidative mutagens is not obtained with strains deficient in either katG or ahpCF, two OxyR-regulated genes. Strain IC206, a derivative of WP2 uvrA carrying a deletion of the umuDC genes and deficient in the MutY glycosylase, has also been added to the WP2 test for the detection of SOS-independent mutations promoted by 8-oxoguanine lesions. Induction of these mutations was observed after treatment with BuOOH, but not after MD or 4NQO exposure. The two new strains, IC203 and IC206, can be useful for the screening of mutations resulting from oxidative stress as well as in studies on antioxidants preventing mutagenesis.

DNA-Binding Proteins↗
PubMed1999

Distinct responses of a recA::luxCDABE Escherichia coli strain to direct and indirect DNA damaging agents.

The recombinant Escherichia coli strain DPD2794 containing a recA::luxCDABE fusion is used to detect genotoxicity of various chemicals. Genotoxic agents were previously categorized into two groups, Direct DNA Damaging (DDD) agents and Indirect DNA Damaging (IDD) agents; these two groups have been distinguished with this strain. Minimum detectable concentrations of the DDD agents were about one to five orders of magnitude lower than those of the IDD agents. The response patterns of this strain to DDD agents differed from those to IDD agents in terms of kinetics and the forms of the dose-dependent response.

DNA Damage↗
PubMed1999

Impact of dimethyl sulfoxide and examples of combined genotoxicity in the SOS chromotest.

The bacterial SOS chromotest with Escherichia coli PQ37 was used for the assessment of genotoxicity of combined xenobiotic treatments. The modulation of test compound genotoxicity by dimethyl sulfoxide (DMSO), a common solvent for test compounds, was assessed as well. It was shown that DMSO modulated SOS chromotest genotoxicity of several xenobiotics: in comparison to test compound dissolution in water, the commonly used addition of 3.2% (v/v) DMSO as solvent lead to a significant increase in the genotoxicity of K(2)RhCl(5) and beta-propiolactone (BPL). However, the effects of cisplatin decreased significantly when DMSO was added. Thus, albeit DMSO is not genotoxic in this test itself, it can interfere with SOS chromotest responses. Further experiments were performed in the absence of DMSO. BPL and cisplatin in combination showed an over-additive synergism in SOS genotoxicity as well as K(2)RhCl(5) and cisplatin did. Addition of Pd(NH(3))(4)Cl(2) and NaAsO(2), which are non-genotoxic in the SOS chromotest, did not enhance the K(2)RhCl(5)- or BPL-mediated SOS sfiA induction. Nevertheless, at the highest subcytotoxic dose of NaAsO(2) tested (200 microM), a slight yet significant suppression of BPL-mediated SOS genotoxicity was observed. These results confirm that the SOS chromotest is a useful tool for the rapid evaluation of the combined genotoxicity of compound mixtures. However, the use of DMSO as test solvent has to be taken with caution.

Cisplatin↗
PubMed1999

SOS induction of selected naturally occurring substances in Escherichia coli (SOS chromotest).

Naturally occurring substances were tested for genotoxicity using a modified laboratory protocol of the Escherichia coli PQ37 genotoxicity assay (SOS chromotest) in the presence and in the absence of an exogenous metabolizing system from rat liver S9-mix. Aristolochic acid I, II, the plant extract aristolochic acid and psoralene were genotoxic; cycasine, emodine, monocrotaline and retrorsine were classified as marginal genotoxic in the SOS chromotest in the absence of S9-mix. In the presence of an exogenous metabolizing system from rat liver S9-mix aristolochic acid I, the plant extract, beta-asarone, cycasin, monocrotaline, psoralen and retrorsine showed genotoxic effects; aristolochic acid II marginal genotoxic effects. Arecoline, benzyl acetate, coumarin, isatidine dihydrate, reserpine, safrole, sanguinarine chloride, senecionine, senkirkine, tannin and thiourea revealed no genotoxicity in the SOS chromotest either in the presence or in the absence of an exogenous metabolizing system from rat liver S9-mix. For 17 of 20 compounds, the results obtained in the SOS chromotest could be compared to those obtained in the Ames test. It was found that 12 (70.6%) of these compounds give similar responses in both tests (6 positive and 6 negative responses). The present investigation and those reported earlier, the SOS chromotest, using E. coli PQ37, was able to detect correctly most of the Salmonella mutagens and non-mutagens.

Alkaline Phosphatase↗
PubMed2002

Molecular mechanisms of adaptive response to alkylating agents in Escherichia coli and some remarks on O(6)-methylguanine DNA-methyltransferase in other organisms.

Alkylating agents are environmental genotoxic agents with mutagenic and carcinogenic potential, however, their properties are also exploited in the treatment of malignant diseases. O(6)-Methylguanine is an important adduct formed by methylating agents that, if not repaired, can lead to mutations and death. Its repair is carried out by O(6)-methylguanine DNA-methyltransferase (MTase) in an unique reaction in which methyl groups are transferred to the cysteine acceptor site of the protein itself. Exposure of Escherichia coli cells to sublethal concentrations of methylating agents triggers the expression of a set of genes, which allows the cells to tolerate DNA lesions, and this kind of inducible repair is called the adaptive response. The MTase of E. coli, encoded by the ada gene was the first MTase to be discovered and one of best characterised. Its repair and regulatory mechanisms are understood in considerable detail and this bacterial protein played a key role in identification of its counterparts in other living organisms. This review summarises the nature of alkylation damage in DNA and our current knowledge about the adaptive response in E. coli. I also include a brief mention of MTases from other organisms with the emphasis on the human MTase, which could play a crucial role in both cancer prevention and cancer treatment.

Adaptation, Physiological↗
PubMed2002

A model for the structure of the Escherichia coli SOS-regulated UmuD2 protein.

The ubiquitous Y-family of DNA polymerases, exemplified by the Escherichia coli UmuC protein (the catalytic subunit of DNA Pol V), possess the remarkable ability to replicate imperfect DNA templates that cannot be replicated by other types of DNA polymerases. Since this ability comes at the cost of a reduced fidelity, it is important that organisms manage these unique polymerases to coordinate their actions with those of the replication machinery. In E. coli, it is becoming evident that a sophisticated series of protein-protein interactions involving the two forms of the umuD gene product, UmuD and UmuD' and components of the replicative DNA polymerase serve to manage the actions of the umuC-encoded DNA polymerase. The purpose of this study was to better understand how structural differences between UmuD2 and UmuD2' help to determine which biological role the umuDC gene products will play; the UmuD2C complex functions as a DNA damage checkpoint effector, while the UmuD2'C complex participates in translesion DNA synthesis, which serves as the mechanistic basis for most chemical and UV light mutagenesis. Based on the results of a combination of disulfide cross-linking experiments, measurements of solvent accessibility and electron paramagnetic spin resonance (EPR) studies, we have developed a refined model for the structure of the UmuD2 homodimer. In the model that we are proposing, the N-terminal arms of UmuD (residues 1-39) form an extended interface in the UmuD2 homodimer by folding down over the globular domains of their intradimer partners. As a result, significant portions of the surface of each globular domain are buried in the UmuD2 homodimer. Based on the structure of the UmuD2' homodimer, both in the crystal and in solution, these same surfaces are exposed. Implications of these structural differences between the UmuD2 and the UmuD2' homodimers with respect to their roles in managing the actions of the umuC-encoded DNA polymerase are discussed.

Binding Sites↗
PubMed2002

Survival and SOS induction in cisplatin-treated Escherichia coli deficient in Pol II, RecBCD and RecFOR functions.

Cisplatin is a potent anticancer agent forming intrastrand-crosslinks in DNA. The efficacy of cisplatin in chemotherapy can be limited by the development of tumor resistances such as elevated DNA repair or damage tolerance. In Escherichia coli, cisplatin treatment causes induction of the SOS regulon resulting in elevated levels of DNA Pol II, DNA Pol IV, DNA Pol V, the cell division inhibitor SfiA (SulA), homologous recombination (HR) and DNA repair. In this work, the roles of Pol II and HR in facilitating resistance of E. coli to cisplatin are studied. SOS induction levels were measured by beta-galactosidase assays in cisplatin-treated and untreated E. coli PQ30 that has the lacZ gene fused to the sfiA promoter. Comparative studies were carried out with derivatives of PQ30 constructed by P1 transduction that have transposon insertions in the polB gene, the recB gene blocking the RecBCD pathway of HR and genes of the RecFOR pathway of HR. Resistance of E. coli strains to cisplatin as determined by plating experiments decreased in the following order: parent PQ30 strain, polB > recO, recR, recF > recB. Both the RecBCD and RecFOR pathways of HR are important for survival when E. coli is exposed to cisplatin, because treatment of double mutants deficient in both pathways reduced colony forming ability to 37% in 6-9min in comparison to 39-120min for single mutants. Pol II and RecF appear to function in two distinct pathways to initiate replication blocked due to damage caused by cisplatin because function of Pol II was required for survival in mutants deficient in the RecFOR pathway after 2h of cisplatin treatment. In contrast, Pol II was not required for survival in recB mutants. SOS induction was delayed in RecFOR deficient mutants but occurred at high levels in the recB mutant soon after cisplatin treatment in a RecFOR-dependent way. An SfiA independent, DNA damage dependent pathway is apparently responsible for the filamentous cells observed after cisplatin or MMC treatments of these SfiA defective strains.

Antineoplastic Agents↗