Ž . Mutation Research 446 1999 155–165 www.elsevier.comrlocatergentox Community address: www.elsevier.comrlocatermutres Effect of various concentrations of acyclovir on cell survival and micronuclei induction on cultured HeLa cells Ganesh Chandra Jagetia ) , R. Aruna Department of Radiobiology, Kasturba Medical College, Manipal, Karnataka 576 119, India Received 22 June 1999; received in revised form 10 August 1999; accepted 24 August 1999 Abstract Ž . The HeLa cells were treated with 0, 0.01, 0.1, 1, 10 and 100 mM acyclovir ACV for 8 h duration and the growth kinetics, cell survival and micronuclei induction were determined. Treatment of HeLa cells with various concentrations of ACV resulted in a concentration-dependent decline in growth kinetics, cell proliferation indices and cell survival. ACV, 100 mM, completely inhibited cell division, where no appreciable changes in cell number were observed from 1 to 5 days post-treatment. This is reflected in cell survival, where the surviving fraction of cells was reduced to 1r2 at 100 mM ACV. Conversely, the frequency of micronuclei showed a concentration-dependent elevation at 20, 30 and 40 h post-treatment. ACV not only induced one micronuclei-bearing binucleate cell but also binucleate cells bearing two and multiple micronuclei in a concentration-dependent manner. The micronuclei frequency increased with time up to 30 h post-treatment and declined thereafter. The relationship between micronuclei induction and cell survival was determined by plotting the former on Y- and the latter on X-axes, respectively. The surviving fraction of cells declined with the elevation in micronuclei frequency and a best fit was observed for linear quadratic formalism. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Acyclovir; HeLa cells; Growth kinetics; Cell survival; Micronuclei; Cell proliferation index 1. Introduction w Ž . Acyclovir 9- 2-hydroxyethoxymethyl guanine, x ACV is a synthetic purine nucleoside analog, syn- thesized at Wellcome Research Laboratories in an wx attempt to search for new anticancer compounds 1 . However, it has been found to be a potent inhibitor Ž . of herpes simplex virus types I and II HSV I and II ) Corresponding author. Tel.: q91-8252-71200 to 71219 ext. 2122; fax: q91-8252-70062; e-mail: info@kmc.ernet.in Ž . and varicella zoster VZV , and has also been re- ported to possess extremely low toxicity for the w x normal host cells 1,2 . ACV has been reported to be non-mutagenic in w x Ames test 3,4 . Similarly, ACV treatment did not increase chromosomal aberrations and sister chro- matid exchanges in cultured peripheral blood lym- w x phocytes of man 5,6 . Since ACV is a guanine nucleoside analogue, a constituent of DNA, it was desired to study the effect of various concentrations of ACV on clonogenicity and micronuclei formation in HeLa cells. 1383-5718r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S1383-5718 99 00159-X