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

Mourelatos, C.; Nikolaropoulos, S.; Fousteris, M.; Pairas, G.; Argyraki, M.; Lykidis, D.; Fidani, S.; Mourelatos, D.; Lialiaris, T.

Mutation Research. Genetic Toxicology and Environmental Mutagenesis 766: 42-45

2014

ISSN/ISBN: 1879-3592
PMID: 24680952
DOI: 10.1016/j.mrgentox.2014.03.005
Accession: 055084536
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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.

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