Tissue‐specific induction of sister chromatid exchanges by ethyl carbamate in mice

Roberts, Gladwin T.; Allen, James W.

doi:10.1002/em.2860020104

Cited by 33 publications

(7 citation statements)

References 43 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…injections of urethane at 50 to 400 mg/kg (Roberts and Allen, 1980). Dose-related increases in SCEs have been found in bone marrow and liver cells of mice following i.p.…”

Section: )mentioning

confidence: 99%

“…To date, the only direct evidence that urethane causes DNA damage in vivo in germ cells has been provided by Roberts and Allen (1980). These authors showed that urethane caused a dose-dependent increase of SCEs in mouse spermatogonia.…”

Section: ) Germ Cellsmentioning

confidence: 99%

“…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%

See 2 more Smart Citations

Mutagenicity, Metabolism, and DNA Interactions of Urethane

Sotomayor

Collins

1990

Toxicol Ind Health

View full text Add to dashboard Cite

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)

show abstract

“…injections of urethane at 50 to 400 mg/kg (Roberts and Allen, 1980). Dose-related increases in SCEs have been found in bone marrow and liver cells of mice following i.p.…”

Section: )mentioning

confidence: 99%

Section: ) Germ Cellsmentioning

confidence: 99%

Section: Metabolism: Dna Interactionsmentioning

confidence: 99%

See 1 more Smart Citation

Mutagenicity, Metabolism, and DNA Interactions of Urethane

Sotomayor

Collins

1990

Toxicol Ind Health

View full text Add to dashboard Cite

show abstract

“…Urethane is known to be carcinogenic in animals, producing mammary, lung, and liver tumours in rats and mice [16,17]. It is also genotoxic: a single subcutaneous, intraperitoneal (ip) or intravenous injection of 50 mg/kg bwt or more has induced chromosome damage (aberrations, micronuclei or sister chromatid exchanges) in various tissues, including the bone marrow, lungs, blood lymphocytes, spleen, liver cells and sperm of mice, rats, and hamsters [18][19][20][21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

An investigation of male-mediated F1 effects in mice treated acutely and sub-chronically with urethane

Edwards

Anderson

Brinkworth

et al. 1999

Teratog. Carcinog. Mutagen.

View full text Add to dashboard Cite

In order to investigate the alleged potential of paternally administered urethane to cause foetal abnormalities and heritable tumours, male CD‐1 mice were treated with urethane, either acutely by intraperitoneal injection at doses of 1.25 and 1.75 g/kg bodyweight (bwt) or sub‐chronically in the drinking water at 1.25 for 10 weeks and 3.75 mg/ml for 9 weeks or vehicle for the control groups. They were mated to untreated females 1 week later. Uterine contents of half the pregnant females were examined just before full term, while the remaining females were allowed to deliver their litters. The resulting F1 offspring were observed for approximately 18 months and 12 months for acute and sub‐chronic exposures respectively and subjected to necropsy examination. Some of the mice treated acutely with 1.75 g/kg bwt exhibited partial infertility but none of those treated with 1.25 g/kg bwt had an adverse effect on their reproductive ability. There was no genetic effect of acute urethane treatment on male germ cells as indicated by dominant lethality. After birth, there was an increase (P <0.05) in post‐implantation deaths possibly due to perinatal mortality. There was an increased incidence and earlier onset of liver tumours induced in F1 male offspring from Fo males treated with 1.75 g/kg bwt, (20.7% vs. 10.1%, P=0.026) but not in the female offspring. F1 males from both treatment groups had mean bodyweights significantly higher than controls (P <0.01). Some males from each dose group of the acute study were examined using the restriction site mutation assay involving analysis of exon sequences. No mutations were identified in testes, liver or spleen of DNA isolated from the urethane‐treated animals. No reproductive or genetic effects were seen with sub‐chronic treatment at either 1.25 or 3.75 mg/ml urethane nor was there any predisposition of F1 animals to tumours although observation times were shorter. Teratogenesis Carcinog. Mutagen. 19:87–103, 1999. © 1999 Wiley‐Liss, Inc.

show abstract

“…Russell et al [ 19871, using the mouse specific locus mutation assay, found no significant induction of mu-tations by EC in spermatogonial and postspermatogonial stages of male mice. To our knowledge, the only consistent evidence that EC may be genotoxic to mouse spermatogonia has come from Roberts and Allen [1980]. These authors reported that EC induced a low but statistically significant increase in sister chromatid exchanges in mouse spermatogonia.…”

Section: Introductionmentioning

confidence: 96%

Induction of DNA damage by urethane in mouse testes: DNA binding and unscheduled DNA synthesis

Sotomayor

Sega

Kadlubar

1994

Environ and Mol Mutagen

View full text Add to dashboard Cite

The extent and persistence of DNA damage and repair were investigated in mouse spermatogenic cells exposed in vivo to urethane (ethyl carbamate, EC). Adult male mice exposed to [3H]EC at 10-1,000 mg/kg were sacrificed 12 hr later. EC/metabolite binding to liver and testicular DNA and to sperm heads from the vasa deferentia was measured. Other male mice were exposed to EC at 50-750 mg/kg, and unscheduled DNA synthesis (UDS) induction was investigated in early spermatid stages. Similar experiments were conducted with vinyl carbamate (VC; putative EC metabolite) at 10-75 mg/kg. [3H]EC bound to liver and testicular DNA and to whole sperm heads. Testicular DNA binding increased linearly with dose, although binding was at least 2 orders of magnitude lower than with liver DNA. Sperm head binding also increased linearly with dose. Dose response studies with the UDS assay showed that EC and VC induced a small but significant increase of the UDS response in early spermatid stages. However, the induced UDS responses were quite variable and did not consistently increase with the administered dose. To determine the time kinetics of UDS induction, [3H]dThd was injected at various times after treatment with 500 mg/kg of EC or 60 mg/kg of VC. A slight but significant UDS increase was observed 4 hr after treatment with EC but not with VC. Overall, these results suggest that EC metabolites bind to testis DNA and cause low-level DNA damage in mouse spermatogenic cells. This type of DNA damage apparently does not have significant genetic consequences.

show abstract

Tissue‐specific induction of sister chromatid exchanges by ethyl carbamate in mice

Cited by 33 publications

References 43 publications

Mutagenicity, Metabolism, and DNA Interactions of Urethane

Mutagenicity, Metabolism, and DNA Interactions of Urethane

An investigation of male-mediated F1 effects in mice treated acutely and sub-chronically with urethane

Induction of DNA damage by urethane in mouse testes: DNA binding and unscheduled DNA synthesis

Contact Info

Product

Resources

About