Comparison of bleomycin and radiation in the G2 assay of chromatid breaks

Purpose: To compare bleomycin with radiation in the G2 chromatid break assay. Controversy exists in the literature about whether G2 bleomycin chromatid‐break sensitivity links with cancer predisposition in the same way as the G2 chromatid radiosensitivity test (the so‐called ‘G2 assay’). Although bleomycin is referred to as a ‘radiomimetic’ agent, it differs from radiation in the way the damage is induced. Materials and methods: Epstein–Barr virus‐immortalized lymphoblastoid cell lines from two head and neck squamous cell carcinoma patients, two breast cancer patients, two ataxia‐telangiectasia patients and two normal control persons were used. Chromosomal damage was determined in cells exposed to 0.3‐Gy radiation or 5 mU ml−1 bleomycin. The numbers of chromatid breaks per cell and of aberrations per cell (i.e. breaks and gaps) were determined. Results: A strong positive correlation was found between the two different damage inducers (r=0.99; p<0.001). This correlation was similar for both the breaks per cell and the total aberrations per cell. Inclusion of gaps in the scoring of chromatid breaks was associated with a higher variability of the data, but this did not influence the outcome of this study. Conclusions: Both bleomycin and radiation give the same sensitivity phenotypes as determined by the G2 assay of chromatid breaks. Thus, when no radiation facility is present, bleomycin seems to be a good alternative to radiation for this type of assay.

[1]  C. Mothersill,et al.  Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition , 2003, British Journal of Cancer.

[2]  C. Leemans,et al.  Involvement of cell cycle control in bleomycin‐induced mutagen sensitivity , 2002, Environmental and molecular mutagenesis.

[3]  A. Thompson,et al.  Chromosomal radiosensitivity in G2-phase lymphocytes identifies breast cancer patients with distinctive tumour characteristics , 2001, British Journal of Cancer.

[4]  T. Kręcicki,et al.  Microsatellite and chromosome instability in squamous cell laryngeal carcinoma. , 2001, International journal of oncology.

[5]  S. Roberts,et al.  Chromosomal radiosensitivity as a marker of predisposition to common cancers? , 2001, British Journal of Cancer.

[6]  S. Roberts,et al.  Sensitivity to radiation-induced chromosome damage may be a marker of genetic predisposition in young head and neck cancer patients , 2001, British Journal of Cancer.

[7]  G. Snow,et al.  Mutagen sensitivity as a biomarker for second primary tumors after head and neck squamous cell carcinoma. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[8]  J. Hain,et al.  Increased G2 chromosomal radiosensitivity in cancer patients: the role of cdk1/cyclin-B activity level in the mechanisms involved. , 2000, International journal of radiation biology.

[9]  P. Bryant,et al.  Production of chromatid breaks by single dsb: evidence supporting the signal model. , 2000, International journal of radiation biology.

[10]  D. Evans,et al.  Heritability of cellular radiosensitivity: a marker of low-penetrance predisposition genes in breast cancer? , 1999, American journal of human genetics.

[11]  D. Boomsma,et al.  Inherited susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes. , 1999, Journal of the National Cancer Institute.

[12]  S. Roberts,et al.  Increased chromosomal radiosensitivity in breast cancer patients: a comparison of two assays. , 1999, International journal of radiation biology.

[13]  P. Lou,et al.  Increased mutagen sensitivity in patients with head and neck cancer is less pronounced in patients with nasopharyngeal carcinoma. , 1998, Archives of otolaryngology--head & neck surgery.

[14]  N. Bundred,et al.  Genetic predisposition to breast cancer. , 1998, The British journal of surgery.

[15]  T. Kręcicki,et al.  Chromosome instability in head and neck cancer patients. , 1997, Oncology reports.

[16]  G. Snow,et al.  Influence of the antioxidant N-acetylcysteine and its metabolites on damage induced by bleomycin in PM2 bacteriophage DNA. , 1996, Carcinogenesis.

[17]  G. Snow,et al.  Increased mutagen sensitivity in head‐and‐neck squamous‐cell carcinoma patients, particularly those with multiple primary tumors , 1994, International journal of cancer.

[18]  P. Byrd,et al.  Genetic and cellular features of ataxia telangiectasia. , 1994, International journal of radiation biology.

[19]  D. Johnston,et al.  Sensitivity to genotoxic effects of bleomycin in humans: Possible relationship to environmental carcinogenesis , 1989, International journal of cancer.

[20]  R. Parshad,et al.  Factors affecting and significance of G2 chromatin radiosensitivity in predisposition to cancer. , 1989, International journal of radiation biology.

[21]  K. Johanson,et al.  Bleomycin, in contrast to gamma irradiation, induces extreme variation of DNA strand breakage from cell to cell. , 1987, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[22]  H. Umezawa,et al.  Characterization of bleomycin action on DNA. , 1975, The Journal of antibiotics.