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Micronuclei frequency induced by bleomycin in human peripheral lymphocytes: correlating BLHX polymorphism with
Francesca Maffei1, Fabio Carbone, Sabrina Angelini
1Department of Pharmacology, University of Bologna, via Irnerio 48, 40126 Bologna, Italy. francesca.maffei@unibo.it
Mutation Research
|December 18, 2007
Summary
The bleomycin hydrolase (BLHX) gene polymorphism influences cancer susceptibility by affecting chromosome damage. Individuals with the BLHX A/A genotype show lower bleomycin-induced DNA damage, suggesting a role in cancer risk assessment.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- Mutagen sensitivity assays, measuring chromosome damage from bleomycin, are explored as cancer susceptibility biomarkers.
- A single nucleotide polymorphism (SNP A1450G) in the bleomycin hydrolase (BLHX) gene is a candidate for variations in mutagen sensitivity.
Purpose of the Study:
- To investigate the impact of BLHX genotype on bleomycin-induced chromosome damage.
- To determine if BLHX polymorphism affects mutagen sensitivity in healthy volunteers.
Main Methods:
- Assessed mutagen sensitivity using bleomycin treatment of peripheral lymphocytes from 45 healthy volunteers.
- Measured chromosome damage via micronuclei (MN) frequencies in cytokinesis-blocked lymphocytes.
- Genotyped subjects for the BLHX gene (A1450G polymorphism).
Main Results:
- No significant difference in spontaneous micronuclei (MN) was found between BLHX genotypes (A/A vs. A/G or G/G).
- Subjects with the BLHX A/A genotype exhibited significantly lower bleomycin-induced MN frequencies compared to carriers of variant alleles (A/G or G/G).
- Multiple regression analysis confirmed BLHX genotype's significant effect on bleomycin-induced damage, independent of age.
Conclusions:
- The BLHX A1450G polymorphism significantly influences individual mutagen sensitivity to bleomycin.
- BLHX genotype may serve as a predictive biomarker for cancer susceptibility by modulating DNA damage response.
