Comparison of the carcinogenic potential of streptozotocin by polarography and alkaline elution.
The carcinogenic potential of streptozotocin (STZ) was evaluated by the polarographic determination of its reduction potential in the presence of alpha-lipoic acid and detection of DNA single-strand brakes by alkaline elution. After STZ electrochemical reduction in an anhydrous solvent, the half-wave potential (E1/2 ) was determined to be -1.340 V. The parameter of the carcinogenic potential (tg alpha) for STZ was 0.400. This is in good agreement with WHO data regarding STZ carcinogenicity. Additionally, it is in the good agreement with the tg alpha value determined for the positive control used, N-nitroso-N-methylurea (NMU), which was found to be 0.459. The 3 hours exposure of A549 human lung tumor cells to 250, 500, and 1000 nmol/ml STZ was followed by DNA single-strand brakes detection using the alkaline elution method. NMU, the positive control, was tested under identical experimental conditions at the same concentrations. Without metabolic activation, NMU induced a significant formation of DNA single-strand brakes only at 1000 nmol/ml. In the presence of the metabolic activation, NMU caused a significant, concentration-dependent formation of DNA single-strand brakes. In the absence of metabolic activation, STZ induced no significant formation of DNA single-strand brakes at any concentration used. In the presence of metabolic activation, STZ caused a significant, concentration-dependent formation of DNA single-strand brakes. The results of this study underline the crucial role of using a metabolic activation system when carcinogenic potential of drugs and chemicals is investigated in vitro studies. Results of polarographic experiments and alkaline elution correlate well with each other and they indicate that these methods are useful to early predict the carcinogenic potential of STZ and other xenobiotics.
Faculty of Medicine, Kuwait University, Safat 13110, Kuwait. cojocel@hsc.kuniv.edu.kw
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Cojocel
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Novotny
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Vachalkova
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Knauf
D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology; D008770:Methylnitrosourea / Q000633:toxicity; D011048:Polarography; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology; D013311:Streptozocin / Q000633:toxicity*
D002273:Carcinogens; D013311:Streptozocin; D008770:Methylnitrosourea; D011065:Poly(ADP-ribose) Polymerases; D008550:Melatonin