Discrimination between genotoxicity and cytotoxicity for the induction of DNA double-strand breaks in cells treated with aldehydes and diepoxides

Vock, Esther; Lutz, Werner; Ilinskaya, О. N.; Vamvakas, Spiros

doi:10.1016/s1383-5718(99)00038-8

Cited by 37 publications

(22 citation statements)

References 21 publications

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“…Repair-proficient pso7/cox11 mutants were found highly sensitive to the mutagens NDEA, an alkylating chemical that is metabolized via redox cycling to yield hydroxylamine radicals, ROS and LP [88,101,102] and to 8-hydroxyquinoline (8HQ), which may also be activated via altered oxygen metabolism [103] and possibly form diol-epoxide derivatives [104,105]. It should be noticed that pso6/erg3 mutants were also sensitive to NDEA, but not to 8HQ, most probably due to the inability of 8HQ to cause LP [103].…”

Section: Pso Genes That Are Involved In Mutagen Metabolism and Not Inmentioning

confidence: 99%

Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae

Brendel

Bonatto

Strauss

et al. 2003

Mutation Research/Reviews in Mutation Research

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Section: Pso Genes That Are Involved In Mutagen Metabolism and Not Inmentioning

confidence: 99%

Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae

Brendel

Bonatto

Strauss

et al. 2003

Mutation Research/Reviews in Mutation Research

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“…(37) stated that DEO was more carcinogenic and mutagenic than the other analogues. The DEO mutagen reacts preferentially with the N 7 of guanosine and the N 3 of adenine, then induces both mono-adducts and inter-strand cross-links by specific genotoxic pathway in absence of cell death, (34,37).…”

Section: Discussionmentioning

confidence: 99%

“…However, it has been employed here as a new selection system for the isolation of new A. niger nitrate assimilation defective mutants. The mutagen 1, 2, 7, 8-Diepoxyoctane (DEO) is one of the most potent mutagens in a wide variety of mutational test systems, including Salmonella typhimurium (25), Saccharomyces cerevisia (26), A. nidulans (17), and human epithelial cells (34). In addition, Ultraviolet light (UV) has widely been used as a mutagen, where it was able to produce different mutant types in A. niger and A.…”

Section: Introductionmentioning

confidence: 99%

Isolation and growth characterization of chlorate and/or bromate resistant mutants generated by spontaneous and induced foreword mutations at several gene loci in Aspergillus niger

Kanan¹,

Al-Najjar²

2010

Braz. J. Microbiol.

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We aimed her mainly to evaluate the contribution of newly employed bromate selection system, in obtaining new Aspergillus niger nitrate/nitrite assimilation defective mutants, through Ultraviolet treatment (UV), 1, 2, 7, 8-Diepoxyoctane (DEO), phenols mixture (Phx)) and spontaneous treatments. The newly employed bromate selection system was able to specify only two putative novel mutant types designated brn (bromate resistant but chlorate sensitive (RS) strain, which may specify nitrite specific transporter) and cbrn mutants (bromate resistant and chlorate resistant strain, which may specify nitrate/nitrite bispecific system). The most relevant and innovative findings of this research work involve the isolation of the RR (cbrn) mutants (a new type of nitrate assimilation defective mutants), that could be useful for studying the bispecific nitrate /nitrite transporter system. The majority of obtained bromate resistant mutants (93.3% of the total mutants obtained by all treatments) were of the brn type, whereas the remaining percentage (6.76%) was given to cbrn strains. The highest percentages of brn mutant strains (48% and 58.6% of the total RS strains) were obtained with UA after spontaneous and Phx treatment, whereas Trp has generated 29% and 42% of RS strains after UV and DEO treatments, respectively. The obtained ratios of cbrn mutants were higher (i.e. in the range of 8.4%-11.64% of the total bromate mutants) with chemical treatments, especially when U.A or Pro was serving as sole N-sources at 25ºC rather than 37ºC. A 69% mutants` yield of Aspergillus niger mutant strains representing nine gene loci (niaD, cnx-6 loci, nrt and nirA) were selected on the bases of chlorate (600 mM) toxicity. All chlorate resistant mutants were completely sensitive to bromate (250 mM). The niaD mutants showed the highest percentage (73.97%) of chlorate resistant mutants obtained with all tested treatments. The UV treatment has generated the highest ratio (86.9%) of niaD mutants, whereas, the least (61%) was obtained with Phx treatment. The highest percentage of cnx mutants (32%) was obtained with Phx treatment. The DEO treatment as compared to other tested treatments was the best to use for obtaining the highest ratios of either nrt (13.8%) mutants or nirA (1.9%) mutants.

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“…A more prolonged exposure (24-72 hr) of human lung carcinoma A594 cells to BDO 2 (100 mM) caused a loss in cell viability after 72 hr, coupled with a large increase in the number of doublestranded DNA breaks and DNA-DNA crosslinks [Vock et al, 1999]. Prolonged (6 hr or more) BDO 2 (5, 10, and 20 mM) exposure of TK6 lymphoblasts resulted in an increase in the number of nonviable cells; however, the total number of live cells remained relatively constant, indicating that, while a number of cells were dying, there was sufficient cellular replication to maintain a relatively constant number of viable cells [Yadavilli and Muganda, 2004].…”

Section: Discussionmentioning

confidence: 99%

Acute exposure of human lung cells to 1,3-butadiene diepoxide results in G1 and G2 cell cycle arrest

Schmiederer

Knutson

Muganda³

et al. 2005

Environ. Mol. Mutagen.

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1,3-Butadiene (BD) causes genetic damage, including adduct formation, sister chomatid exchange, and point mutations. Previous studies have focused on the types of genetic damage and tumors found after long-term exposure of rodents to butadiene. This study examined the effect of the most active BD metabolite, butadiene diepoxide (BDO2), on cell cycle entry and progression in human lung fibroblasts (LU cells) with a normal diploid karyotype. Serum-arrested (G0) LU cells were exposed to BDO2 for 1 hr and stimulated to divide with medium containing 10% fetal bovine serum. The BDO2-treated LU cells were evaluated for cell cycle progression, nuclear localization of arrest mediators, mitotic index, and cellular proliferation. The BDO2-treated cells demonstrated a substantial inhibition of cell proliferation when treated with 100 microM BDO2 for 1 hr. No appreciable levels of apoptosis or mitotic figures were observed in the BDO2-treated cells through 96 hr posttreatment. Flow cytometric analysis revealed that the lack of proliferation in BDO2-treated LU cells was related to G1 arrest in about half of the cells and a delayed progression through S and G2 arrest in nearly all of the remaining cells. Both G1 and G2 arrest were prolonged and only a very small percentage of BDO2-treated cells were eventually able to replicate. Increased nuclear localization of both p53 and p21(cip1) was observed in BDO2-treated cells, suggesting that the cell cycle arrest was p21(cip1)-mediated. These results demonstrate that BDO2 induces cell cycle perturbation and arrest even with short-term exposure that does not produce other pathologic cellular effects.

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Discrimination between genotoxicity and cytotoxicity for the induction of DNA double-strand breaks in cells treated with aldehydes and diepoxides

Cited by 37 publications

References 21 publications

Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae

Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae

Isolation and growth characterization of chlorate and/or bromate resistant mutants generated by spontaneous and induced foreword mutations at several gene loci in Aspergillus niger

Acute exposure of human lung cells to 1,3-butadiene diepoxide results in G1 and G2 cell cycle arrest

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