Evidence for excision repair-dependent and -independent processes in ara C-induced chromosome rearrangements in G1 human lymphocytes.
1-beta-D-arabinofuranosylcytosine (ara C) enhances the formation of chromosome rearrangements such as translocations or dicentric chromosomes in G1 cells containing DNA lesions. The formation of rearrangements is hypothesized to be the result of inhibition of excision repair. Ara C has also been known to lead to the formation of chromosome rearrangements in G1 cells in the absence of induced DNA lesions. It is not known whether a common mechanism is involved in these two processes. In the present study, we used excision repair-deficient XP cells to investigate whether excision repair is involved in the formation of chromosome rearrangements in G1 cells which do not contain induced DNA lesions. G0 Lymphocytes from an XP patient were either treated with 4-nitroquinoline-1-oxide (4NQO) or left untreated. Cells were then cultured in the presence of ara C for about 18 h. Aphidicolin (APC), which induces chromosome rearrangements in cells containing 4NQO-induced DNA lesions, was used for comparison. The resulting frequency of dicentrics and rings (dic & ring) was determined at the first mitoses after culture initiation. In 4NQO-pretreated XP cells, the frequency of dic & ring was not increased by post-treatment with ara C or with APC. This result is thought to reflect the absence of excision repair in XP cells. However, normal induction of dic & ring was observed in XP cells not pretreated with 4NQO but treated with ara C. Thus, there seems to be two different processes involved in the induction of G1 rearrangements: excision repair-dependent and excision repair-independent. UV-endonuclease is not involved in excision repair-independent rearrangements.
Kishi
K
K
School of Health Sciences, Kyorin University Tokyo, Japan.
Sekizawa
K
K
D000293:Adolescent; D000328:Adult; D002648:Child; D002869:Chromosome Aberrations / Q000235:genetics*; D003561:Cytarabine / Q000494:pharmacology*; D004260:DNA Repair / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure*; D019384:Nucleic Acid Synthesis Inhibitors; D012854:Sister Chromatid Exchange; D014983:Xeroderma Pigmentosum / Q000235:genetics
D019384:Nucleic Acid Synthesis Inhibitors; D003561:Cytarabine