title: Potentiation by caffeine of cytogenetic damage induced by steroidal derivatives in human lymphocytes in vitro.
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.
authors.affiliation: Laboratory of Genetics, Medical Faculty, Demokritos University of Thrace, Alexandroupolis 68100, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Mourelatos
authors.affiliation: Laboratory of Pharmaceutical Chemistry, University of Patras, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Nikolaropoulos
authors.affiliation: Laboratory of Pharmaceutical Chemistry, University of Patras, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Fousteris
authors.affiliation: Laboratory of Pharmaceutical Chemistry, University of Patras, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Pairas
authors.affiliation: Laboratory of Biology and Genetics, Medical Faculty, Aristotle University of Thessaloniki, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Argyraki
authors.affiliation: Laboratory of Genetics, Medical Faculty, Demokritos University of Thrace, Alexandroupolis 68100, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Lykidis
authors.affiliation: Laboratory of Biology and Genetics, Medical Faculty, Aristotle University of Thessaloniki, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Fidani
authors.affiliation: Laboratory of Biology and Genetics, Medical Faculty, Aristotle University of Thessaloniki, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Mourelatos
authors.affiliation: Laboratory of Genetics, Medical Faculty, Demokritos University of Thrace, Alexandroupolis 68100, Greece. Electronic address: lialiari@med.duth.gr.
authors.forename: Th
authors.initials: T
authors.lastname: Lialiaris
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000819:agonists / Q000494:pharmacology; D002110:Caffeine / Q000009:adverse effects / Q000819:agonists / Q000494:pharmacology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000819:agonists / Q000494:pharmacology; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009588:Nitrogen Mustard Compounds / Q000009:adverse effects / Q000819:agonists / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013256:Steroids / Q000009:adverse effects / Q000819:agonists / Q000494:pharmacology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000697:Central Nervous System Stimulants; D009588:Nitrogen Mustard Compounds; D013256:Steroids; D002110:Caffeine
keywords: Caffeine; Cultured human lymphocytes; Nitrogen mustards; Proliferation rate index; Sister chromatid exchanges; Synergism