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Hyperthermia can differentially modulate the repair of doxorubicin-damaged DNA in normal and cancer cells*.

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Blasiak J., Widera K., Pertyński T.

Hyperthermia can modulate the action of many anticancer drugs, and DNA repair processes are temperature-dependent, but the character of this dependence in cancer and normal cells is largely unknown. This subject seems to be worth studying, because hyperthermia can assist cancer therapy. A 1-h incubation at 37°C of normal human peripheral blood lymphocytes and human myelogenous leukemia cell line K562 with 0.5 μM doxorubicin gave significant level of DNA damage as assessed by the alkaline comet assay. The cells were then incubated in doxorubicin-free repair medium at 37°C or 41°C. The lymphocytes incubated at 37°C needed about 60 min to remove completely the damage to their DNA, whereas at 41°C the time required for complete repair was shortened to 30 min. There was also a difference between the repair kinetics at 37°C and 41°C in cancer cells. Moreover, the kinetics were different in doxorubicin-sensitive and resistant cells. Therefore, hyperthermia may significantly affect the kinetics of DNA repair in drug-treated cells, but the magnitude of the effect may be different in normal and cancer cells. These features may be exploited in cancer chemotherapy to increase the effectiveness of the treatment and reduce unwanted effects of anticancer drugs in normal cells and fight DNA repair-based drug resistance of cancer cells.

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 Pertyński T.

1 Czechowska A.

1 Drzewoski J.

1 Kołacińska A.

1 Morawiec Z.

1 Przybyłowska K.

1 Rykała J.

1 Widera K.

1 Zadrożny M.

Search results

Hyperthermia can differentially modulate the repair of doxorubicin-damaged DNA in normal and cancer cells*.

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