Genotoxicity and cytotoxicity in male B6C3F1 mice following exposure to mixtures of 1,3-butadiene and styrene

Leavens, Teresa L.; Farris, Georgia M.; James, R. Arden; Shah, Rekha S.; Wong, Victoria A.; Marshall, Marianne W.; Bond, James A.

doi:10.1002/(sici)1098-2280(1997)29:4<335::aid-em1>3.0.co;2-9

Cited by 12 publications

(4 citation statements)

References 36 publications

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“…Many other organic solvents were also mainly catalysed by CYP2E1, e.g. chloroform ( 77), acetone ( 30), trichloroethylene ( 78–80), trichloroethane ( 80), styrene ( 81), benzene ( 82) and xylene ( 82).…”

Section: Drugs and Other Organic Compoundsmentioning

confidence: 99%

Cytochrome P450 2E1: its clinical and toxicological role

2000

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Cytochrome (CYP) P450 2E1 is clinically and toxicologically important and it is constitutively expressed in the liver and many other tissues. In contrast to many other CYP isoenzymes, indisputable evidence for a functionally important polymorphism of CYP2E1 in the human population is lacking. CYP2E1 metabolizes a wide variety of chemicals with different structures, in particular small and hydrophobic compounds, including potential cytotoxic and carcinogenic agents. In addition, chlorzoxazone and trimethadione metabolism are good CYP2E1 probes for liver disease in vivo and in vitro. In the future, methods for fully analysing the function of CYP2E1 using knockout mice will be established. This article reviews recent advances in our understanding of the role of human CYP2E1 in drug metabolism.

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Section: Drugs and Other Organic Compoundsmentioning

confidence: 99%

Cytochrome P450 2E1: its clinical and toxicological role

2000

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“…Heptadecane, eicosane and n-butyl acetate were present as the most predominant component in the oleoresins (acetone and ethyl acetate extracts), and have been reported to have anti-inflammatory and antimicrobial effects [ 37 ] cytotoxic effects on HeLa and MCF-7 cell lines, and antimicrobial, larvicidal [ 38 ] and cytotoxic [ 39 ] properties, respectively. Styrene was also reported as genotoxic, cytotoxic and mutagenic [ 40 , 41 , 42 , 43 ], and has been detected in high amounts in ethyl acetate extract in the current investigation. p -Cresol and fatty acid constituents of linoleic, linolenic acid and l -ascorbyl 2,6-dipalmitate were present in a relatively significant amount in essential oil.…”

Section: Discussionmentioning

confidence: 58%

Chemical Composition and Cytotoxic Activity of the Essential Oil and Oleoresins of In Vitro Micropropagated Ansellia africana Lindl: A Vulnerable Medicinal Orchid of Africa

2021

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Orchids are rich treasure troves of various important phytomolecules. Among the various medicinal orchids, Ansellia africana stands out prominently in the preparing of various herbal medicines due to its high therapeutic importance. The nodal explants of A. africana were sampled from asymbiotically germinated seedlings on basal Murashige and Skoog (MS) medium and were micropropagated in MS medium supplemented with 3% sucrose and 10 µM meta topolin (mT) + 5 µM naphthalene acetic acid (NAA) +15 µM indole butyric acid (IBA) + 30 µM phloroglucinol (PG). In the present study, the essential oil was extracted by hydrodistillation and the oleoresins by the solvent extraction method from the micropropagated A. africana. The essential oil and the oleoresins were analysed by Gas Chromatography (GC) and GC/MS (Mass spectrometry). A total of 84 compounds were identified. The most predominant components among them were linoleic acid (18.42%), l-ascorbyl 2,6-dipalmitate (11.50%), linolenic acid (10.98%) and p-cresol (9.99%) in the essential oil; and eicosane (26.34%), n-butyl acetate (21.13%), heptadecane (16.48%) and 2-pentanone, 4-hydroxy-4-methyl (11.13%) were detected in the acetone extract; heptadecane (9.40%), heneicosane (9.45%), eicosane (6.40%), n-butyl acetate (14.34%) and styrene (22.20%) were identified and quantified in the ethyl acetate extract. The cytotoxic activity of essential oil and oleoresins of micropropagated A. africana was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide) assay on Vero cells compared to the standard drug doxorubicin chloride. The present research contains primary information about the therapeutic utility of the essential oil and oleoresins of A. africana with a promising future research potential of qualitative and quantitative improvement through synchronised use of biotechnological techniques.

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“…The hematopoietic system is a target for butadiene-induced effects in rodents, based on the observation of lymphocytic lymphomas (NTP, 1993), cytogenetic effects in bone marrow (Cunningham etal., 1986;Irons etal., 1986aIrons etal., , 1987Tice etal., 1987;NTP, 1993;Leavens et al, 1997), and suppression of stem-cell differentiation (Irons et al, 1996). Aneuploidy, which is believed to be associated with leukemia in humans, has been induced in human lymphocytes exposed in vitro to the mono-and diepoxide metabolites of butadiene (Vlachodimitropoulos et al, 1997;Xi et al, 1997).…”

Section: Carcinogenicity and Genotoxicitymentioning

confidence: 64%

“…With respect to effects on somatic cells, although butadiene was mutagenic at the hprt locus in both mice and rats (Cochrane & Skopek, 1993, 1994Tates et al, 1994Tates et al, , 1998Meng et al, 1998Meng et al, , 2000, its mutagenic potency was greater in mice (Meng et al, 1998(Meng et al, , 2000. Other manifestations of genotoxicity (chromosomal aberrations, sister chromatid exchanges, micronuclei, and DNA binding or damage) were noted in somatic cells of mice but not in those of rats exposed to much higher concentrations Cunningham et al, 1986;Irons et al, 1986aIrons et al, , 1986bIrons et al, , 1987Kreiling et al, 1986;Tice et al, 1987;Jauhar et al, 1988;Arce et al, 1990;Shelby, 1990;Victorin et al, 1990;NTP, 1993;Przygoda et al, 1993;Vangala et al, 1993;Adler et al, 1994;Autio et al, 1994;Walles et al, 1995;Sorsa et al, 1996;Anderson et al, 1997;Koivisto et al, 1997Koivisto et al, , 1998Leavens et al, 1997;Stephanou et al, 1998;Tretyakova et al, 1998aTretyakova et al, , 1998b. However, unlike the observations with the parent compound, there is little evidence of species differences in the sensitivity to genotoxic effects in somatic or germ cells induced by the epoxide metabolites of butadiene (EB, DEB, and EBdiol), although there was some indication of interstrain variability (Conner et al, 1983;Sharief et al, 1986;Walk et al, 1987;…”

Section: Carcinogenicity and Genotoxicitymentioning

confidence: 99%

1,3-Butadiene: Exposure Estimation, Hazard Characterization, and Exposure-Response Analysis

Hughes

Walker

et al. 2003

Journal of Toxicology and Environmental Health, Part B

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1,3-Butadiene has been assessed as a Priority Substance under the Canadian Environmental Protection Act. The general population in Canada is exposed to 1,3-butadiene primarily through ambient air. Inhaled 1,3-butadiene is carcinogenic in both mice and rats, inducing tumors at multiple sites at all concentrations tested in all identified studies. In addition, 1,3-butadiene is genotoxic in both somatic and germ cells of rodents. It also induces adverse effects in the reproductive organs of female mice at relatively low concentrations. The greater sensitivity in mice than in rats to induction of these effects by 1,3-butadiene is likely related to species differences in metabolism to active epoxide metabolites. Exposure to 1,3-butadiene in the occupational environment has been associated with the induction of leukemia; there is also some limited evidence that 1,3-butadiene is genotoxic in exposed workers. Therefore, in view of the weight of evidence of available epidemiological and toxicological data, 1,3-butadiene is considered highly likely to be carcinogenic, and likely to be genotoxic, in humans. Estimates of the potency of butadiene to induce cancer have been derived on the basis of both epidemiological investigation and bioassays in mice and rats. Potencies to induce ovarian effects have been estimated on the basis of studies in mice. Uncertainties have been delineated, and, while there are clear species differences in metabolism, estimates of potency to induce effects are considered justifiably conservative in view of the likely variability in metabolism across the population related to genetic polymorphism for enzymes for the critical metabolic pathway.

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Genotoxicity and cytotoxicity in male B6C3F1 mice following exposure to mixtures of 1,3-butadiene and styrene

Cited by 12 publications

References 36 publications

Cytochrome P450 2E1: its clinical and toxicological role

Cytochrome P450 2E1: its clinical and toxicological role

Chemical Composition and Cytotoxic Activity of the Essential Oil and Oleoresins of In Vitro Micropropagated Ansellia africana Lindl: A Vulnerable Medicinal Orchid of Africa

1,3-Butadiene: Exposure Estimation, Hazard Characterization, and Exposure-Response Analysis

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