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Free radical scavengers can modulate the DNA-damaging action of alloxan.

100%

Blasiak J., Sikora A., Czechowska A., Drzewoski J.

2003

vol. 50

issue 1

205-210

Alloxan can generate diabetes in experimental animals and its action can be associated with the production of free radicals. It is therefore important to check how different substances often referred to as free radical scavengers may interact with alloxan, especially that some of these substance may show both pro- and antioxidant activities. Using the alkaline comet assay we showed that alloxan at concentrations 0.01-50 μM induced DNA damage in normal human lymphocytes in a dose-dependent manner. Treated cells were able to recover within a 120-min incubation. Vitamins C and E at 10 and 50 μM diminished the extent of DNA damage induced by 50 μM alloxan. Pre-treatment of the lymphocytes with a nitrone spin trap, α-(4-pyridil-1-oxide)- N-t-butylnitrone (POBN) or ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), which mimics glutathione peroxides, reduced the alloxan-evoked DNA damage. The cells exposed to alloxan and treated with formamidopyrimidine-DNA glycosylase (Fpg) and 3-methyladenine-DNA glycosylase II (AlkA), enzymes recognizing oxidized and alkylated bases, respectively, displayed greater extent of DNA damage than those not treated with these enzymes. The results confirmed that free radicals are involved in the formation of DNA lesions induced by alloxan. The results also suggest that alloxan can generate oxidized DNA bases with a preference for purines and contribute to their alkylation.

Analysis of the G/C polymorphism in the 5'-untranslated region of the RAD51 gene in breast cancer.

64%

Blasiak J., Przybyłowska K., Czechowska A., Zadrożny M., Pertyński T., Rykała J., Kołacińska A., Morawiec Z., Drzewoski J.

2003

vol. 50

issue 1

249-253

The breast cancer suppressor proteins BRCA1 and BRCA2 interact with RAD51, a protein essential for maintaining genomic stability by playing a central role in homology-dependent recombinational repair of the DNA double-strand breaks. Therefore, genetic variability in the RAD51 gene may contribute to the appearance and/or progression of breast cancer. A single nucleotide polymorphism in the 5'- untranslated region of RAD51 (a G to C substitution at position 135, the G/C polymorphism) is reported to modulate breast cancer risk. We investigated the distribution of genotypes and frequency of alleles of the G/C polymorphism in breast cancer. Tumor tissues were obtained from postmenopausal women with node-negative and node-positive breast carcinoma with uniform tumor size. Blood samples from age matched healthy women served as control. The G/C polymorphism was determined by PCR-based MvaI restriction fragment length polymorphism. The distribution of the genotypes of the G/C polymorphism did not differ significantly (P >0.05) from those predicted by the Hardy-Weinberg distribution. There were no differences in the genotype distribution and allele frequencies between node-positive and node-negative patients. There were no significant differences between distributions of the genotypes in subgroups assigned to histological grades according to Scarf-Bloom-Richardson criteria and the distribution predicted by Hardy-Weinberg equilibrium (P >0.05). Our study implies that the G/C polymorphism of the RAD51 gene may not be directly involved in the development and/or progression of breast cancer and so it may not be useful as an independent marker in this disease.

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2 Acta Biochimica Polonica

2 2003

2 Blasiak J.

2 Czechowska A.

2 Drzewoski J.

1 Kołacińska A.

1 Morawiec Z.

1 Pertyński T.

1 Przybyłowska K.

1 Rykała J.

1 Sikora A.

1 Zadrożny M.

Search results

Free radical scavengers can modulate the DNA-damaging action of alloxan.

Analysis of the G/C polymorphism in the 5'-untranslated region of the RAD51 gene in breast cancer.