Mutation Research, 92 (1982) 379-392 379
Elsevier Biomedical Press
Effects of aphidicolin on repair replication and
induced c h r o m o s o m a l aberrations in m a m m a l i a n cells
A.A. van Zeeland t,2, C.J.M. Bussmann 1, F. Degrassi i,
A.R. Filon 1,2 A.C. van Kesteren-van Leeuwen 1
F. Palitti 1,3 and A.T. Natarajan 1,2
t Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, Wassenaarseweg
72, 2333 A L Leiden (The Netherlands), -' J.A. Cohen lnteruniversity Institute for Radiopathologv and
Radiation Protection, Leiden (The Netherlands), and 3 Centro di Genetica Evoluzionistica, lstituto di
Genetica, Universitd di Roma, Rorna (Italy)
(Received 15 September 1981)
(Accepted 22 September 1981 )
Summary
The influence of aphidicolin, an inhibitor of polymerase a, on UV-induced repair
replication in human skin fibroblasts, as well as in HeLa cells, was determined. In
growing fibroblasts and in HeLa cells, aphidicolin had a potentiating effect on
UV-induced repair replication, whereas in fibroblasts grown to confluency, aphi-
dicolin had an inhibitory effect. This inhibitory effect was stronger when measured
in the presence of hydroxyurea. In HeLa cells the presence of both aphidicolin and
hydroxyurea also had an inhibitory effect, but in the presence of hydroxyurea alone,
UV-induced repair replication was enhanced. The results of these studies can be
explained on the basis of differences in deoxyribonucleotide triphosphate pool sizes
in growing and confluent cells.
Post-treatment of X-irradiated human lymphocytes in the G O and G~ stages with
aphidicolin increased the frequencies of X-ray-induced chromosomal aberrations.
Such an increase was not observed in G~ cells of CHO after similar treatment with
X-rays and aphidicolin. However, treatment with aphidicolin, in the G 2 stage, of
CHO cells that had been exposed to UV or alkylating agents in the G~ stage
increased the frequencies of induced chromatid breaks. The significance of these
results is discussed.
Abbreviations: APC, aphidicolin; AraC, arabinoside cytosine; BUdR, 5-bromodeoxyuridine; FUdR,
5-fluorodeoxyuridine; HU, hydroxyurea; MMC, mitomycin C; MMMC, monofunctional mitomycin C;
4-NQO, 4-nitroquinoline l-oxide.
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