Supplementation of melatonin protects human lymphocytes in vitro from the genotoxic activity of melphalan.
Melatonin (MLT) is a natural oncostatic factor of the human body as well as an antioxidant thus protects the nuclear DNA from oxidative damage. It also has the ability to reduce the side effects of various drugs when used as a combination therapy. The anti-neoplastic agent melphalan (MEL), which encompasses a number of side effects, is a strong alkylating agent and a potent inducer of sister chromatid exchanges (SCEs). The aim of the current in vitro study was to investigate the ability of MLT to reduce the genotoxic effect of MEL on normal human cultured peripheral lymphocytes. Cells were treated with both agents at various concentrations (MLT 100, 200 and 400 microM and MEL 330, 490 and 650 nM) and incubated for 72 h prior harvesting. The levels of cytostaticity, cytotoxicity and genotoxicity were qualitatively evaluated using the proliferation rate index, the mitotic index and the SCE methodology, respectively. Our results demonstrated the protective effect of MLT on cells treated with MEL in vitro. The greatest protective effect of MLT at 100 and 400 microM was illustrated against 330 nM of MEL in comparison with all other doses of MEL. These observations imply that MLT may be proved useful in reducing some of the toxic effects associated with certain classes of chemotherapeutic agents and other chemical and physical mutagens and carcinogens, acting both as an antioxidant-radical scavenger and a protective mechanism against cellular damage due to exposure to free radical-producing agents. It is essential to investigate substances with protective properties which are normally produced from the human body.
Lialiaris
Theodore
T
Department of Genetics, Medical School, Demokritus University of Thrace, Alexandroupolis 68100, Greece. lialiari@med.duth.gr
Lyratzopoulos
Emmanuel
E
Papachristou
Fotini
F
Simopoulou
Maria
M
Mourelatos
Constantinos
C
Nikolettos
Nikolaos
N
D018906:Antineoplastic Agents, Alkylating / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D019610:Cytoprotection; D004249:DNA Damage; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology*; D008558:Melphalan / Q000037:antagonists & inhibitors* / Q000633:toxicity
D018906:Antineoplastic Agents, Alkylating; D000975:Antioxidants; D008550:Melatonin; D008558:Melphalan