Review of the mutagenicity of ethylene oxide

Dellarco, Vicki L.; Generoso, W.M.; Sega, Gary A.; Fowle, J R; Jacobson‐Kram, David

doi:10.1002/em.2850160207

Cited by 83 publications

(24 citation statements)

References 75 publications

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“…Ethene also is produced endogeneously. The genetic toxicity and animal carcinogenicity of EtO is well documented, and human occupational exposure to EtO has been associated with an increased risk of leukemia (36). The mutagenic effect of EtO in the HPRT gene in human diploid fibroblasts was demonstrated recently by Kolman et al (25).…”

Section: Ethylene Oxide-induced Hprt Mutationmentioning

confidence: 98%

Mutations induced in the hypoxanthine phosphoribosyl transferase gene by three urban air pollutants: acetaldehyde, benzo[a]pyrene diolepoxide, and ethylene oxide.

Lambert

Andersson

Bastlová

et al. 1994

Environ Health Perspect

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Provisional mutational spectra at the hypoxanthine phosphoribosyl transferase (HPRT) locus in vitro have been worked out for acetaldehyde (AA) and benzo[alpyrene diolepoxide (BPDE) in human (T)-lymphocytes and for ethylene oxide (EtO) in human diploid fibroblasts using Southern blotting and polymerase chain reaction (PCR)-based DNA sequencing techniques. The results indicate that large genomic deletions are the predominating hprt mutations caused by AA and EO, whereas BPDE induces point mutations that are mainly GC>TA transversions. The mutational spectra induced by the three agents are clearly different from the background spectrum in human T-cells. Thus, the hprt locus is a useful target for the study of chemical-specific mutational events that may help identify causes of background mutation in human cells in vivo. -Environ Health Perspect 102(Suppl 4): 135-138 (1994).

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Section: Ethylene Oxide-induced Hprt Mutationmentioning

confidence: 98%

Mutations induced in the hypoxanthine phosphoribosyl transferase gene by three urban air pollutants: acetaldehyde, benzo[a]pyrene diolepoxide, and ethylene oxide.

Lambert

Andersson

Bastlová

et al. 1994

Environ Health Perspect

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“…Although exposure limits have been set for EtO in the workplace, an upward trend in exposures exceeding the short-term exposure limit has been observed in a recent survey of U.S. hospitals, suggesting that there may be a parallel increase in short-term peak exposures to workers not detected by personal monitoring [LaMontagne et al, 2004]. Since a dose-rate effect of EtO has been demonstrated in experimental mice under conditions of constant total dose [Generoso et al, 1986;Dellarco et al, 1990], our results may have important implications for workers exposed directly or incidentally to the short-term EtO peak exposures in the workplace in terms of adduct formation.…”

Section: Discussionmentioning

confidence: 99%

“…EtO has been shown to be mutagenic and genotoxic in a variety of biological systems, including the induction of gene mutations, sister chromatid exchanges (SCE), chromosomal aberrations, and micronuclei in both experimental animals and occupationally exposed workers [Dellarco et al, 1990;IARC, 1994;Kolman et al, 2002]. The International Agency for Research on Cancer has classified EtO as a human carcinogen based largely on animal and mechanistic data from cytogenetic studies [IARC, 1994].…”

Section: Introductionmentioning

confidence: 99%

“…EtO is a direct-acting alkylating agent which forms adducts with cellular macromolecules, including proteins and DNA, without requiring metabolic activation [Dellarco et al, 1990;Segerback, 1990;IARC, 1994]. N7-(2 0 -hydroxyethyl)guanine (N7-HEG), which represents about 90% of the alkylated sites, is the major DNA adduct induced in vitro [Segerback, 1990;Li et al, 1992] and in experimental animals [Segerback, 1983;Walker et al, 1993;Wu et al, 1999;van Sittert et al, 2000].…”

Section: Introductionmentioning

confidence: 99%

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DNA adducts in granulocytes of hospital workers exposed to ethylene oxide

Yong¹,

Schulte²,

Kao³

et al. 2007

American J Industrial Med

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This study has demonstrated for the first time, detectable levels of N7-HEG adducts in granulocytes of hospital workers with EtO exposures at levels less than the current U.S. standard of 1 ppm (8-hr TWA). A nonsignificant increase in adduct levels with increasing EtO exposure indicates that further studies of EtO-exposed workers are needed to clarify the relationship between EtO exposure and N7-HEG adduct formation.

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“…EtO is a strained molecule with a residual positive charge (electrophilic) and has the ability to rapidly alkylate critical nucleophiles such as DNA. EtO has repeatedly been shown to be a mutagen and clastogen to somatic and germ cells [see Dellarco et al, 1990 for review]. Controlling short-term.…”

Section: Ntroductl Onmentioning

confidence: 99%

Induction of sister chromatid exchange in spleen and bone marrow cells of rats exposed by inhalation to different dose rates of ethylene oxide

Ong

Xing

et al. 1993

Environ and Mol Mutagen

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We investigated the effects of dose rate on the frequency of sister chromatid exchange (SCE) in bone marrow and spleen cells of rats exposed to ethylene oxide (EtO). Four groups (18/group) of male Fischer 344 rats were exposed to EtO by inhalation. The exposures consisted of 100 ppm for 6 hr/day, 300 ppm for 2 hr/day, 600 ppm for 1 hr/day, and clean air control. All EtO treated rats were given a total exposure dose of 600 ppm.hr daily, 5 days/week for 3, 6, or 9 months. Six rats per group were sacrificed at each time point, and SCEs were measured in cultured spleen and bone marrow cells. A statistically significant increase was found in SCEs in both bone marrow and spleen cells for all treated groups and at each time point when compared to the control, except at the 3-month exposure for the middle and high dose-rate groups in bone marrow cells. In the spleen, the increases in SCEs were similar among the three experimental groups. In bone marrow, the lowest dose rate (100 ppm) resulted in higher SCE frequencies than the medium and high dose-rate group after 3 and 6 month exposures. The overall frequencies of SCEs in the spleen cells were higher than in the bone marrow cells. The increase in SCE frequencies and decrease in the replicative index in spleen cells were also dependent on the duration of exposure. These results indicate that (1) EtO, by inhalation, can cause SCEs both in spleen and bone marrow cells of Fischer 344 rats, (2) spleen cells are more sensitive to EtO than bone marrow cells, and (3) in bone marrow cells the lowest dose-rate (longest) exposure causes more SCEs than the highest dose-rate (shortest) exposures.

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Review of the mutagenicity of ethylene oxide

Cited by 83 publications

References 75 publications

Mutations induced in the hypoxanthine phosphoribosyl transferase gene by three urban air pollutants: acetaldehyde, benzo[a]pyrene diolepoxide, and ethylene oxide.

Mutations induced in the hypoxanthine phosphoribosyl transferase gene by three urban air pollutants: acetaldehyde, benzo[a]pyrene diolepoxide, and ethylene oxide.

DNA adducts in granulocytes of hospital workers exposed to ethylene oxide

Induction of sister chromatid exchange in spleen and bone marrow cells of rats exposed by inhalation to different dose rates of ethylene oxide

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