چکیده (انگلیسی):

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 M), although at low
concentrations (≤200 M) 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 M) 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.