Amifostine protection against mitomycin-induced chromosomal breakage in fanconi anaemia lymphocytes.
Fanconi anaemia (FA) is a rare genetic chromosomal instability syndrome caused by impairment of DNA repair and reactive oxygen species (ROS) imbalance. This disease is also related to bone marrow failure and cancer. Treatment of these complications with radiation and alkylating agents may enhance chromosomal breakage. We have evaluated the effect of amifostine (AMF) on basal and mitomycin C (MMC)-induced chromosomal breakage in FA blood cells using the micronucleus assay. The basal micronuclei count was higher among FA patients than healthy subjects. Pre-treatment with AMF significantly inhibited micronucleation induced by MMC in healthy subjects (23.4 +/- 4.0 - MMC vs 12.3 2.9 - AMF --> MMC) MN/1000CB, p < 0.01, one way ANOVA) as well as in FA patients (80.0 +/- 5.8 - MMC vs 40.1 +/- 5.8 - AMF --> MMC) MN/1000CB, p < 0.01, ANOVA). Release of ROS by peripheral blood mononuclear cells treated with AMF -> MMC and measured by chemoluminometry showed that AMF-protection was statistically higher among FA patients than in healthy individuals. Based on these results we suggest that AMF prevents chromosomal breakage induced by MMC, probably by its antioxidant effect.
Camelo
Ricardo M
RM
Department of Pharmacology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, CEP 31270-901, Brazil.
Kehdy
Fernanda S G
FS
Salas
Carlos E
CE
Lopes
Miriam T P
MT
D000293:Adolescent; D000328:Adult; D004999:Amifostine / Q000494:pharmacology*; D001773:Blood Cells; D016022:Case-Control Studies; D002648:Child; D019457:Chromosome Breakage / Q000187:drug effects*; D005199:Fanconi Anemia / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D016685:Mitomycin / Q000009:adverse effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D016685:Mitomycin; D004999:Amifostine
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