Potentiation by caffeine of cytogenetic damage induced by steroidal derivatives in human lymphocytes in vitro.

C Mourelatos, S Nikolaropoulos, M Fousteris, G Pairas, M Argyraki, D Lykidis, S Fidani, D Mourelatos, Th Lialiaris

Journal: Mutation research. Genetic toxicology and environmental mutagenesis 2014;766():42-5

PMID: 24680952

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Abstract

We studied the effects of three newly synthesized steroidal derivatives of nitrogen mustards, alone or in combination with caffeine, on sister chromatid exchange (SCE) frequencies and on human lymphocyte proliferation kinetics. The agents have as alkylator functionalities either P-N,N-bis(2-chloroethyl)aminophenyl-buturate (CHL) or P-N,N-bis(2-chloroethyl)aminophenyl-acetate (PHE), esterified with a modified steroidal nucleus. An enhancement of SCE frequency was seen with compounds which contain either PHE or CHL as alkylators and are esterified with a steroidal nucleus having added a cholestene group in the 17-position of the D-ring. The exocyclic insertion of an -NHCO- group in the D-ring of the steroidal nucleus esterified with PHE (amide ester of PHE) gave a compound showing increased SCE frequency. Enhanced cytogenetic damage was observed when lymphocytes were exposed in vitro to caffeine. The compounds, alone or in combination with caffeine, caused a concentration-dependent increase in SCE frequencies and cell division delays, and caffeine was found to act synergistically with the steroidal alkylators.

Address: Laboratory of Genetics, Medical Faculty, Demokritos University of Thrace, Alexandroupolis 68100, Greece.; Laboratory of Pharmaceutical Chemistry, University of Patras, Greece.; Laboratory of Biology and Genetics, Medical Faculty, Aristotle University of Thessaloniki, Greece.; Laboratory of Genetics, Medical Faculty, Demokritos University of Thrace, Alexandroupolis 68100, Greece. Electronic address: [email protected].

DOI: 10.1016/j.mrgentox.2014.03.005

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MeSH Terms: Adult, Antineoplastic Agents, Alkylating, Caffeine, Cell Nucleus, Central Nervous System Stimulants, Chromosome Aberrations, Drug Synergism, Female, Humans, Lymphocytes, Male, Nitrogen Mustard Compounds, Sister Chromatid Exchange, Steroids