Antioxidant N-acetyl cysteine reduces incidence and multiplicity of lymphoma in Atm deficient mice

Abstract

Hereditary human disorder ataxia telangiectasia (AT) is characterized by an extremely high incidence of lymphoid malignancies, neuromotor dysfunction, immunodeficiency and radiosensitivity. Cells from AT patients show genetic instability and a continuous state of oxidative stress. We examined the effect of long-term dietary supplementation with the thiol-containing antioxidant, N-acetyl- l-cysteine (NAC), on survival and cancer formation in Atm (AT-mutated) deficient mice, used as an animal model of AT. NAC was chosen because it is well-tolerated in animals and humans. It can be used by the oral route and for long-term at high concentrations. In addition, NAC suppresses carcinogenesis-associated biological markers in Atm deficient mice, such as DNA deletions and oxidative DNA damage (R. Reliene, E. Fischer, R.H. Schiestl, Effect of N-acetyl cysteine on oxidative DNA damage and the frequency of DNA deletions in atm-deficient mice, Cancer Res. 64 (2004) 5148–5153). In this study, NAC significantly increased the lifespan and reduced both the incidence and multiplicity of lymphoma in Atm deficient mice. The life span increased from 50 to 68 weeks and the incidence of lymphoma decreased by two-fold (76.5% versus 37.5%). Moreover, in mice with lymphoma, multiplicity of tumors decreased from 4.6 to 2.8 tumors per mouse. Thus, dietary supplementation with NAC may turn out to be protective against lymphomagenesis in AT patients.