Carcinogenesis, Vol 19, 791-796, Copyright © 1998 by Oxford University Press
H Kimura, T Takada, Y Shingu, Y Kato, H Iyehara-Ogawa and T Terado
Spontaneous mutations and neocarzinostatin-induced mutations were
investigated in the hypoxanthine-guanine phosphoribosyltransferase (hprt)
gene in exponentially growing Chinese hamster ovary cells. Neocarzinostatin
(NCS) treatment caused an 4.5-fold increase in mutation frequency. Analysis
by multiplex polymerase chain reaction and sequencing of hprt cDNA revealed
that spontaneous mutations in this system were characterized by a
relatively high rate of large deletions and double-base substitutions, and
a low rate of splice mutations compared with data reported in fibroblastic
cell lines. NCS hardly affected this spectrum of spontaneous mutations,
which indicates the rare incidence of NCS-specific change in the
exponential growth phase. This is in contrast to aprt gene mutations
reported in plateau phase cells in which base substitutions occur
preferentially at sites affected by NCS. These results suggest that
differences in the loci assayed or in the processes involved in mammalian
mutagenesis in the exponential growth phase and the plateau phase may be
the source of the different results.
ARTICLES
Neocarzinostatin-induced mutations at the hprt locus in exponentially growing CHO cells, compared with spontaneous mutations
Department of Experimental Radiology, Shiga University of Medical Science, Otsu, Japan. kimurah@belle.shiga-med.ac.jp
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