Delay of the excision of UV light-induced DNA adducts is involved in the coclastogenicity of UV light plus arsenite.
Chromatid exchanges and chromatid breaks were synergistically increased by a 2-h post-treatment with arsenite (VS treatment) but not with arabinofuranosyl cytosine (VA treatment) of UV-irradiated late-G1 Chinese hamster ovary cells. In order to determine the mechanism of this UV-arsenite coclastogenicity, we have compared the effects of arsenite and arabinofuranosyl cytosine on the generation of DNA strand breaks in UV-irradiated cells by alkaline elution and alkaline sucrose sedimentation. Only very small numbers of DNA breaks were detected immediately after VS treatment, however the breaks in parental strands increased as the cells reached mitosis in drug-free medium, whereas a large number of breaks were detected immediately after VA treatment but the breaks decreased thereafter. By labelling the newly synthesized DNA, we have also shown that the VS-treated cells had more breaks in daughter strands than the VA-treated cells at the time of reaching mitosis. The effect of a 2-h post-treatment with arsenite on the excision of UV-induced DNA adducts was further investigated by using the exponentially growing cells. The results confirmed that very low amount of breaks was detectable immediately after VS treatment, however the amount of breaks increased upon the removal of arsenite. Therefore, the breaks in the daughter strands of VS-treated cells may come from DNA replication using templates containing unexcised adducts, or using broken templates. It is conceivable that gaps in the overlapping regions of parental and daughter strands may result in chromatid breaks and that misreplication, because of unexcised adducts or gaps in the parental strands, may result in chromatid exchanges.
Wang
T C
TC
Institute of Zoology, Academia Sinica, Taipei, ROC.
Huang
J S
JS
Yang
V C
VC
Lan
H J
HJ
Lin
C J
CJ
Jan
K Y
KY
D000818:Animals; D018053:Arsenites / Q000008:administration & dosage*; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000528:radiation effects*; D018736:DNA Adducts / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D066298:In Vitro Techniques; D016296:Mutagenesis; D014466:Ultraviolet Rays
D018053:Arsenites; D018736:DNA Adducts; D003561:Cytarabine; D004247:DNA; C015001:arsenite