Neoplasma Vol.50, p.110-116, 2003
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Title: Comparision of the carcinogenic potential of streptozotocin by polarography and alkaline elution
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Author: C., COJOCEL
; L., NOVOTNY
; A, VACHALKOVA
; B., KNAUF
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Abstract: 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.
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Keywords: Streptozotocin, polarography, alkadine elution, single-stranded DNA, carcinogenicity.
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Year: 2003, Volume: 50, Issue: |
Page From: 110, Page To: 116 |
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