Cytotoxicity test and cytogenetic analysis of effects of aminoguanidine in vitro.
The potential genotoxic activity of chemical substances in vitro is usually assessed by the micronucleus test and by karyological analysis. Use of the fluorescent plus Giemsa (FPG) technique is also recommended in the event that positive results are found in the micronucleus test, or if there is an increased rate of structural and numerical chromosome aberrations compared with controls. The tested substance, aminoguanidine (AG), has a marked ability to inhibit the toxic effects of carbonyl products (carbonyl stress) that arise during the end-phases of non-enzymatic protein glycation both in vitro and in vivo. The importance of this ability follows the finding that the production of advanced glycation end-products (AGE) is a part of the molecular mechanism of the pathogenesis of chronic diabetic complications. The aim of this study was to test the cytotoxic and clastogenic effects of AG on cells of the diploid cell line B-HEF-2, derived from a three-month-old male fetus. The results of the test did not reveal any induction of micronucleus production in the analyzed cells at AG concentrations ranging between 1 x 10(-2) and 1 x 10(-4) mol.L-1. Karyological analysis showed no clastogenic effect of the tested substance nor any increased rate of structural chromosome aberrations. The positive properties of AG and to its potential use as a glycoxidation inhibitor and AGE production are somewhat dimmed by its ionic nature, which hampers hydrophobic interaction with the nonpolar components of biological membranes. For this reason, the authors will further study the cytotoxicity and cytogenetic analysis of Schiff bases of AG synthesis on the basis of natural aldehydes (resorcine aldehyde, pyridoxal, etc.) in which antiglycation activity has been detected.
Vojtassák
J
J
Institute of Medical Biology and Genetics, School of Medicine, Comenius University, Bratislava, Slovak Republic. vojtassak@fmed.uniba.sk
Cársky
J
J
Böhmer
D
D
Braxatorisová
T
T
Geislerová
V
V
Duríková
M
M
Pagácová
E
E
Repiská
V
V
Danisovic
L
L
Blasko
M
M
D002460:Cell Line; D020732:Cytogenetic Analysis / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D006801:Humans; D008297:Male; D015162:Micronucleus Tests / Q000379:methods
D006146:Guanidines; C004479:pimagedine