Genetic effects of formaldehyde in yeast. II. Influence of ploidy and of mutations affecting radiosensitivity on its lethal effects

Chanet, Roland; Izard, C; Moustacchi, E.

doi:10.1016/0027-5107(76)90166-4

Cited by 37 publications

(9 citation statements)

References 19 publications

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“…Thus, it is not surprising that defects in this gene increase sensitivity to a variety of DNA-damaging agents, including UV, the UV-mimetic chemical 4-nitroquinoline-1-oxide, mono-and bifunctional alkylating agents,.and photoactivated psoralens (6,8,9,40,41,49). As well, the RADI gene product is required for the repair of NM-methyladenine (13).…”

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confidence: 99%

Specificity of the mutator effect caused by disruption of the RAD1 excision repair gene of Saccharomyces cerevisiae

et al. 1990

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The product of the RADI gene of the yeast Saccharomyces cerevisiae is believed to function at the incision step of excision repair of DNA damage (9). Thus, it is not surprising that defects in this gene increase sensitivity to a variety of DNA-damaging agents, including UV, the UV-mimetic chemical 4-nitroquinoline-1-oxide, mono-and bifunctional alkylating agents,.and photoactivated psoralens (6,8,9,40,41,49). As well, the RADI gene product is required for the repair of NM-methyladenine (13). Not only do RADI deficiencies sensitize cells to the lethal effects of certain genotoxic agents, but also they enhance UV and 4-nitroquinoline-1-oxide-induced mutagenesis (27, 40) and UV-induced mitotic interchromosomal recombination (45). Recent findings suggest that the RADI gene product also plays a role in mitotic intrachromosomal recombination and in integration of linear DNA molecules into homologous genomic sequences (2,17,44). In addition to these various properties, defects in RADl confer a mutator phenotype (35,43,47). Both enhanced locus reversion to prototrophy and forward mutation to suppression and canavanine resistance have been reported, but neither the precise mutational changes involved nor the specificity of the mutator effect has been elucidated.To account for the association between repair defects and enhanced spontaneous mutagenesis in yeast cells, von Borstel and colleagues (12, 42) have invoked the repair channeling hypothesis (5, 10). According to this hypothesis, impairment of a specific repair pathway results in channeling of damage normally repaired by that pathway along other, competitive pathways. In a similar fashion, shunting of spontaneous DNA lesions through mutagenic repair pathways might account for elevated spontaneous tnutation in repair-deficient strains. However, the nature of these errorprone pathways has remained obscure, and generally the magnitudes of the mutator effects in yeast cells are relatively small. Consequently, it has been suggested that repair defects might have a more indirect influence on spontaneous * Corresponding author. mutation, perhaps by somehow reducing the fidelity. of DNA replication (43) or the efficiency of correcting replication errors (26). Alternatively, the products of some repair genes might play a regulatory role (7,16) so that modulation of processes other than DNA repair could be responsible for the mutator phenotypes of certain repair-deficient mutants.Characterization of the locations and types of DNA sequence alteration occurring spontaneously within a single gene in a radl background would provide valuable infoi-mation about the specificity of the radl mutator effect. In turn, this could yield important clues about the mechanism(s) of enhanced spontaneous mutagenesis in excision repair-deficient strains. To examine mutational specificity, we previously developed a system for the DNA sequence analysis of forward mutations in the yeast tRNA suppressor gene . In this system, all types of base pair substitution as well as deletions, duplications, in...

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confidence: 99%

Specificity of the mutator effect caused by disruption of the RAD1 excision repair gene of Saccharomyces cerevisiae

et al. 1990

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“…Formaldehyde has been shown to cause mutation in various primitive organisms (Kaplan, 1948;Slinzynska, 1957;Nishioka, 1973;Chanet et al, 1976) and in cultured mammalian cells (Gosser and Butterworth, 1977; Obe and Beek, 1979; Ross and Shipley, 1980; Ragan and Boreiko, 1981).…”

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Phenoxyethanol as a nontoxic substitute for formaldehyde in long‐term preservation of human anatomical specimens for dissection and demonstration purposes

et al. 1984

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Formaldehyde has recently been declared a potential carcinogen. Occupational health authorities throughout the world are therefore likely to put stricter regulations to its use also within anatomical disciplines. We have been able to reduce the atmospheric concentration of formaldehyde in our dissection rooms to below the detection limit of a conventional Dräger tube multigas analyzer (i.e., below 0.5 ppm or 0.6 mg formaldehyde/m3 air), by extracting previously formaldehyde-fixed material for more than 3 months in 1% phenoxyethanol in tap water. In this fluid our material has remained soft and flexible with a consistency and color retention suitable for dissection and demonstration purposes for up to 10 years. Fungal attacks are rare and we have been unable to raise bacteria from such specimens. Even the microscopical structure of most tissues remains satisfactory after 5 years in 1% phenoxyethanol. The unpleasant and irritating smell traditionally felt in dissection rooms is almost absent in our facilities, but some of our students still mention slight odor, headache, drowsiness, and mild eye, nose, and throat irritation during their dissection practice periods.

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“…In general, the investigations by other groups contrast with ours in that we employed quantitative and sensitive measures of toxicity (i.e., growth inhibition) at doses closer to environmental exposure (0.6 mM or less), considering endogenous levels of FA in human blood and tissue range from approximately 0.08–0.4 mM (Andersen et al, 2010; Heck and Casanova, 2004; National Toxicology Program (NTP), 2010). Initial studies of FA toxicity in yeast found high concentrations of FA (17–83 mM) increase recombination (Chanet et al, 1975), alter excision repair mutant survival (Chanet et al, 1976), and generate DNA-protein crosslinks (Magana-Schwencke and Ekert, 1978). Although these analyses utilized much higher doses, the results are generally congruent to ours.…”

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confidence: 99%

Functional Toxicogenomic Profiling Expands Insight into Modulators of Formaldehyde Toxicity in Yeast

et al. 2016

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Formaldehyde (FA) is a commercially important chemical with numerous and diverse uses. Accordingly, occupational and environmental exposure to FA is prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, and lymphohematopoietic cancers, have been linked to FA exposure, prompting designation of FA as a human carcinogen by U.S. and international scientific entities. Although the mechanism(s) of FA toxicity have been well studied, additional insight is needed in regard to the genetic requirements for FA tolerance. In this study, a functional toxicogenomics approach was utilized in the model eukaryotic yeast Saccharomyces cerevisiae to identify genes and cellular processes modulating the cellular toxicity of FA. Our results demonstrate mutant strains deficient in multiple DNA repair pathways–including homologous recombination, single strand annealing, and postreplication repair–were sensitive to FA, indicating FA may cause various forms of DNA damage in yeast. The SKI complex and its associated factors, which regulate mRNA degradation by the exosome, were also required for FA tolerance, suggesting FA may have unappreciated effects on RNA stability. Furthermore, various strains involved in osmoregulation and stress response were sensitive to FA. Together, our results are generally consistent with FA-mediated damage to both DNA and RNA. Considering DNA repair and RNA degradation pathways are evolutionarily conserved from yeast to humans, mechanisms of FA toxicity identified in yeast may be relevant to human disease and genetic susceptibility.

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Genetic effects of formaldehyde in yeast. II. Influence of ploidy and of mutations affecting radiosensitivity on its lethal effects

Cited by 37 publications

References 19 publications

Specificity of the mutator effect caused by disruption of the RAD1 excision repair gene of Saccharomyces cerevisiae

Specificity of the mutator effect caused by disruption of the RAD1 excision repair gene of Saccharomyces cerevisiae

Phenoxyethanol as a nontoxic substitute for formaldehyde in long‐term preservation of human anatomical specimens for dissection and demonstration purposes

Functional Toxicogenomic Profiling Expands Insight into Modulators of Formaldehyde Toxicity in Yeast

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