Induction of unscheduled DNA synthesis by chemical mutagens in testicular cells of the mouse in vitro

Beikirch, H.

doi:10.1007/bf00355488

Cited by 21 publications

(7 citation statements)

References 9 publications

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“…These authors showed that urethane caused a dose-dependent increase of SCEs in mouse spermatogonia. Similarly, no significant induction of UDS was observed in mouse testicular cells after in vitro exposure with N-hydroxyurethane (Beikirch, 1977). Based on this evidence, it appears that urethane can reach the testes and cause slight DNA damage in spermatogonia.…”

Section: ) Germ Cellsmentioning

confidence: 78%

“…Excellent reviews have been published on this subject (Mirvish, 1968;IARC, 1974;Miller and Miller, 1983). About 5 to 10% of the dose is excreted in the urine of rats as measured by 14C Nomura (1975) 5.9; 10.7% ntc Nomura (1975Nomura ( , 1982 6.9; 5.3% a See Russell et al (1987) Lavappa and Yerganian (1 97 1) synergism for CA in F, Cumming et al (1978) no synergism for CA in (-1 (-1 Roberts andAllen (1980) Sotomayor et al (1987) Wyrobek and Bruce (1975) Topham (1981) Beikirch (1977 analysis (Boyland and Rhoden, 1949). About 5 to 10% of the dose is excreted in the urine of rats as measured by 14C Nomura (1975) 5.9; 10.7% ntc Nomura (1975Nomura ( , 1982 6.9; 5.3% a See Russell et al (1987) Lavappa and Yerganian (1 97 1) synergism for CA in F, Cumming et al (1978) no synergism for CA in (-1 (-1 Roberts andAllen (1980) Sotomayor et al (1987) Wyrobek and Bruce (1975) Topham (1981) Beikirch (1977 analysis (Boyland and Rhoden, 1949).…”

Section: Metabolism: Dna Interactionsmentioning

confidence: 99%

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Mutagenicity, Metabolism, and DNA Interactions of Urethane

Sotomayor

Collins

1990

Toxicol Ind Health

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Urethane, a known animal carcinogen, has been the subject of intensive research efforts spanning 40 years. Recent concerns have focused on the presence of urethane in a variety of fermented foods and alcoholic beverages, although no epidemiological studies or human case reports have been published. Much information is available about the mutagenesis, metabolism, and DNA interactions of urethane in experimental systems. Urethane is generally not mutagenic in bacteria although in some instances it acts as a weak mutagen. Urethane is not mutagenic in Nuerospora but is weakly mutagenic in Saccharomyces. Drosophila appear to be the only organisms that consistently give positive mutagenic results with urethane, but its mutagenicity is weak and in many cases shows no clear dose dependence. Urethane is a good clastogen in mammalian somatic cells in vivo, but it shows variable results with cells in vitro. It efficiently induces sister chromatid exchanges in a variety of cells. Mammalian spermatogenic cells are insensitive to the induction of specific locus and dominant lethal mutations by urethane. Mutational synergism has been reported to occur between ethyl methanesulfonate and urethane when administered two generations apart, and some investigators have suggested possible synergism for cancer-causing mutations in mice exposed to X-rays and urethane one generation apart. These studies are controversial and have not been confirmed. Studies on the induction of cancer-causing dominant mutations by urethane are at variance with results from extensive studies with the specific locus test in mice. Urethane studies with the unscheduled DNA synthesis assay in mouse spermatogenic cells and with the sperm abnormality test have given negative results. Urethane is rapidly and evenly distributed in the body. The rate of elimination of urethane from plasma is a saturable process and varies according to the strain and age of the animal. Recent studies have concentrations similar to those in wine, ethanol inhibits the tissue distribution of urethane in mice. These results are important because they suggest a lower carcinogenic/mutagenic risk than expected from exposure to urethane in alcoholic beverages. Although research on the metabolic activation of urethane has been extensive, no conclusive results have been obtained about its active metabolite, at one time thought to be N-hydroxyurethane. More recently, it has been postulated that urethane is activated to vinyl carbamate and that this metabolite is capable of reacting with DNA.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: ) Germ Cellsmentioning

confidence: 78%

Section: Metabolism: Dna Interactionsmentioning

confidence: 99%

Mutagenicity, Metabolism, and DNA Interactions of Urethane

Sotomayor

Collins

1990

Toxicol Ind Health

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“…Thus, a positive or negative result was taken at face value, mainly as indicated by the conclusion of a particular study. In a few cases, the germ-cell stages could not be determined because the incorporation of [ 3 H]dThd was measured in a mixture of spermatogenic cells after hydroxyurea (HU) exposure [Beikirch, 1977]. In others, specific spermatogenic cells were isolated by sedimentation at unit gravity but the purity of the germ-cell fractions was not determined [Lee and Suzuki, 1979].…”

Section: Resultsmentioning

confidence: 99%

Unscheduled DNA synthesis assay in mammalian spermatogenic cells: An update

Sotomayor

Sega

2000

Environ. Mol. Mutagen.

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“…In the unscheduled DNA synthesis test, positive results were reported by Benigni et al (1990) in human fibroblast, whereas no increase was detected in testicular cells isolated from male mice in vitro (Beikirch, 1977) and in HeLa cells (Martin et al, 1978). Matsuda et al (2016) found that aminoacridine has inhibitory effects on the DNA-damage response in human cells; the authors suggested that this could be responsible for the chromosome-damaging potential of the compound.…”

Section: Evaluation Of Genotoxicitymentioning

confidence: 99%

Dyes in aquaculture and reference points for action

Penninks¹,

Baert²,

Levorato³

et al. 2017

EFS2

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The European Commission requested EFSA to evaluate whether a series of dyes are covered by the 'Guidance on methodological principles and scientific methods to be taken into account when establishing Reference Points for Action (RPAs) for non-allowed pharmacologically active substances present in food of animal origin' and to which group they should be attributed according to this guidance. Although these substances are not registered for use in food-producing animals in the European Union, they may be used illegally in aquaculture for their antimicrobial properties. It was concluded that acriflavine, 3-aminoacridine, aminoacridine, basic blue 7, brilliant green, leucobrilliant green, C.I. basic blue 26, chloranil, crystal violet, leucocrystal violet, dichlone, ethyl violet, methylene blue, new methylene blue, Nile blue, pararosaniline base, proflavine, proflavine hydrochloride, rhodamine 6G and trypan red are covered by the guidance document and belong to group I. A toxicological screening value of 0.0025 lg/kg body weight per day is applicable. Azure blue and potassium permanganate were excluded from the evaluation due to their inorganic nature.

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Induction of unscheduled DNA synthesis by chemical mutagens in testicular cells of the mouse in vitro

Cited by 21 publications

References 9 publications

Mutagenicity, Metabolism, and DNA Interactions of Urethane

Mutagenicity, Metabolism, and DNA Interactions of Urethane

Unscheduled DNA synthesis assay in mammalian spermatogenic cells: An update

Dyes in aquaculture and reference points for action

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