Published in Cancer Detection and Prevention 2001; 25(4):369-374.

A Comparative Study on Cytogenetic and Antineoplastic Effects Induced by Two Modified Steroidal Alkylating Agents

Athanasios Papageorgiou, PhD,a Dimtrios Tsavdaridis, MD,b Georgios D. Geromichalos, PhD,a Charalambos Camoutsis, PhD,c Evagelos Karaberis, PhDd Dionysios Mourelatos, PhD,d Eleni Chrysogelou, PhD,a Styianos Houvartas, BSc,c and Alexandros Kotsis, MDd

aLaboratory of Experimental Chemotherapy, Theagenion Anticancer Institute, Thessaloniki, b2nd Hospital IKA, Thessaloniki, cLaboratory of Pharmaceutical Chemistry, University of Patras, and the dDepartment of Medicinal Biology and Genetics, Aristotle University, Thessaloniki, Greece.

Address all correspondence and reprint requests to: Address correspondence and reprint requests to: Dr. D. Mourelaros, MSc, PhD, Department of Medical Biology & Genetics. Aristotle University Thessaloniki 54006 Greece.

ABSTRACT: We investigated the effects of two newly synthesized steroidal derivatives of nitrogen mustard on sister chromatid exchange rates and on human lymphocyte proliferation kinetics. The compound 3β-hydroxy-5α,22α-spirostan-12-one-p- (N,N-bis(2-chloroethyl)amino)phenyacetate(1) was, on a molar basis, less effective in inducing sister chromatid exchange and suppressing cell proliferation rate indices than compound 3β-hydroxy-12α-aza-C-homo-5α,22α-spirostan-12- one-p-(N,N-bis(2-chloroethyl)amino)phenylacetate(2). A correlation was observed between the magnitude of the sister chromatid exchange response and the depression of cell proliferation index. We also studied the effects of the aforementioned compounds on Lewis lung carcinoma. The order of the percent inhibition of tumor growth achieved by the compounds coincides with the order of the cytogenetic effects they induce.

KEY WORDS: cell kinetics, antitumor activity, steroidal alkylators.