Concentration- and time-dependent genotoxicity profiles of isoprene monoepoxides and diepoxide, and the cross-linking potential of isoprene diepoxide in cells.

Yan Li, Avishay Pelah, Jing An, Ying-Xin Yu, Xin-Yu Zhang

Open access · goldAbstract read

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Article in Toxicology reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed, 1 citations in OpenAlex.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Yan LiInstitute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.

Avishay PelahDepartment of Plastics Engineering, Shenkar College of Engineering and Design, Ramat Gan 52526, Israel.

Jing AnInstitute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.

Ying-Xin YuInstitute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.

Xin-Yu ZhangInstitute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China.

Shanghai University · CNShenkar College of Engineering and Design · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Isoprene, a possible carcinogen, is a petrochemical and a natural product being primarily produced by plants. It is biotransformed to 2-ethenyl-2-methyloxirane (IP-1,2-O) and 2-(1-methylethenyl)oxirane (IP-3,4-O), both of which can be further metabolized to 2-methyl-2,2'-bioxirane (MBO). MBO is mutagenic, but IP-1,2-O and IP-3,4-O are not. While IP-1,2-O has been reported being genotoxic, the genotoxicity of IP-3,4-O and MBO, and the cross-linking potential of MBO have not been examined. In the present study, we used the comet assay to investigate the concentration- and time-dependent genotoxicity profiles of the three metabolites and the cross-linking potential of MBO in human hepatocyte L02 cells. For the incubation time of 1 h, all metabolites showed positive concentration-dependent profiles with a potency rank order of IP-3,4-O > MBO > IP-1,2-O. In human hepatocellular carcinoma (HepG2) and human leukemia (HL60) cells, IP-3,4-O was still more potent in inducing DNA breaks than MBO at high concentrations (>200 μM), although at low concentrations (≤200 μM) IP-3,4-O exhibited slightly lower or similar potency to MBO. Interestingly, their time-dependent genotoxicity profiles (0.5-4 h) in L02 cells were different from each other: IP-1,2-O and MBO (200 μM) exhibited negative and positive profiles, respectively, with IP-3,4-O lying in between, namely, IP-3,4-O-caused DNA breaks did not change over the exposure time. Further experiments demonstrated that hydrolysis of IP-1,2-O contributed to the negative profile and MBO induced cross-links at high concentrations and long incubation times. Collectively, the results suggested that IP-3,4-O might play a significant role in the toxicity of isoprene.

Indexed as

2-(1-Methylethenyl)oxirane2-Ethenyl-2-methyloxirane2-Methyl-2,2′-bioxiraneComet assayDEB, 1,2,3,4-diepoxybutaneDMEM, Dulbecco's Modified Eagle's MediumDMSO, dimethyl sulfoxideFBS, fetal bovine serumGenotoxicityHepG2, human hepatocellular carcinoma cellsHL60, human leukemia cellsIMDM, Iscove's Modified Dulbecco's MediumIP-1,2-O, 2-ethenyl-2-methyloxiraneIP-3,4-O, 2-(1-methylethenyl)oxiraneIsopreneIsoprene metabolitesMBO, 2-methyl-2,2′-bioxiranemCPBA, m-chloroperoxybenzoic acidMMS, methyl methanesulfonateMTT, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromidePBMCs, peripheral blood mononuclear cellsSD, standard deviation%Tail DNA, percentage of DNA in the tail

Identifiers

PMID28962224

DOI10.1016/j.toxrep.2014.03.002

PMCPMC5598284

OpenAlexW1983370904

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LicenceCC BY-NC-SA

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.