M. Chovanec et al., REJOINING OF DNA STRAND BREAKS INDUCED BY PROPYLENE-OXIDE AND EPICHLOROHYDRIN IN HUMAN-DIPLOID FIBROBLASTS, Environmental and molecular mutagenesis, 32(3), 1998, pp. 223-228
The repair kinetics of DNA single- and double-strand breaks (SSBs, DSB
s) induced with two carcinogenic epoxides, propylene oxide (PO) and ep
ichlorohydrin (ECH), was studied in human diploid Fibroblasts. The met
hods used were: alkaline DNA unwinding (ADU), the comet assay, and pul
sed Field gel electrophoresis (PFGE). About 70% of SSBs, measured by A
DU, were rejoined after the treatment with 5 mMh and 10 mMh of PO with
in 20 hr, and the half-life was estimated to be similar to 15 hr. On t
he other hand, effective rejoining of SSBs after ECH treatment was obs
erved only at a dose of 1 mMh (a half-life of similar to 15 hr), where
as after 2 mMh treatment, only 26% of SSBs could be rejoined within 20
hr. Furthermore, the use of the comet assay demonstrated that DNA str
and breaks were effectively rejoined after PO and ECH treatment at dos
es of 5-10 mMh and 0.5-1 mMh, respectively. About 76% and 83% of DSBs
induced by 5 and 10 mMh of PO, respectively, were rejoined within 4 hr
after the treatment (a half-life of similar to 2.5 hr), with little f
urther repair thereafter. At lower dose of ECH (1 mMh) a half-life for
DSBs rejoining was estimated to be similar to 2 hr; however, only 29%
of DSBs were rejoined within 2 hr at the higher dose of 2 mMh. After
18 hr, the rejoining following treatment with a lower dose was negligi
ble. At a higher dose, a rapid accumulation of DSBs was observed, prob
ably as the result of cell death and DNA degradation. The results demo
nstrate the capability of human diploid fibroblasts to repair DNA SSBs
and DSBs at low-to-moderate doses of the epoxides. A weak capacity to
rejoin DNA strand breaks induced by higher doses of ECH may be a cons
equence of its higher DNA alkylation activity and approximately 10 tim
es higher toxicity compared to PO. Environ. Mel. Mutagen. 32:223-228,
1998 (C) 1998 Wiley-Liss, Inc.