Cytogenetic analysis of the effects of epinephrine on cultured human lymphocytes

Abstract

Epinephrine can modulate mitotic activity of normal and malignant cells and exhibit genotoxic potential in some test-systems. It is assumed that metabolic conversion of phenolic groups in the catechol ring of epinephrine leads to the formation of reactive derivatives and superoxide anions capable of damaging cellular molecules including DNA. The aim of the present study was to evaluate the cytotoxic and genotoxic effects of epinephrine on human peripheral blood lymphocytes in vitro. The lowest concentration of epinephrine used in these experiments (5x10-10 M) was calculated to be in the range of the physiological blood level of epinephrine in humans. Three experimental concentrations corresponded to minimal (2x10-7 M), average (10-6 M) and maximal (5x10-6 M) therapeutic doses in human medicine. In addition, the highest concentrations exceeded the maximal therapeutic dose 10-fold (5x10-5 M) and 30-fold (1.5x10-4 M), respectively. On the basis of the results obtained it can be concluded that epinephrine had no influence on the appearance of chromosome aberrations under the described experimental conditions. However, mitotic index was significantly lower in cultures treated with the three highest concentrations of epinephrine used in this investigation.

Adrenalin može da promeni mitotsku aktivnost normalnih i malignih ćelija Pored toga, adrenalin ispoljava genotoksične efekte u nekim test-sistemima. Smatra se da metabolička konverzija fenolnih grupa u kateholnom prstenu adrenalina dovodi do stvaranja reaktivnih derivata i superoksidnih anjona sposobnih da oštete molekule u ćeliji, uključujući DNK. Cilj ovog istraživanja bio je da se izvrši evaluacija citotoksičnih i genotoksičnih efakata adrenalina na limfocite periferne krvi čoveka in vitro. Najniža eksperimentalna koncentracija adrenalina korišćena u ovom eksperimentu (5x10-10 M) proračunata je tako da bude uporedljiva sa fiziološkom koncentracijom adrenalina u krvi čoveka. Tri eksperimentalne koncentracije odgovaraju minimalnim (2x10-7 M), srednjim (10-6 M) i maksimalnim (5x10-6 M) terapijskim dozama u humanoj medicini. Pored toga, dve najviše koncentracije veće su od maksimalne terapijske doze deset (5x10-5 M) i trideset puta (1.5x10-4 M). Na osnovu dobijenih rezultata može se zaključiti da adrenalin nije značajno uticao na pojavu hromozomskih aberacija pod opisanim eksperimentalnim uslovima. Međutim, tri najviše koncentracije adrenalina upotrebljene u ovom eksperimentu dovode do značajnog smanjenja mitotske aktivnosti.