DNA-DAMAGE AND REPAIR IN TUMOR AND NONTUMOR TISSUES OF MICE INDUCED BY NICOTINAMIDE

In vivo DNA damage and repair was induced by nicotinamide (NAM) in ade notype 12 virus-induced mouse sarcoma A12B3 and sarcoma F inoculated i nto CBA mice. DNA damage, NAM and NAD concentrations were measured aft er in vivo exposure to NAM, in tumours and spleens by alkaline elution and by HPLC analysis. Our results indicate that NAM between 100-1000 mg kg(-1) causes a high level of in vivo DNA strand breaks in tumours and normal tissues in mice bearing the immunogenic sarcoma A12B3 but n ot in the non-immunogenic sarcoma F. The repair process was also delay ed by the NAM treatment probably owing to inhibition of the DNA repair enzyme, poly(ADP-ribose)polymerase, as evidenced by accumulation of N AM and NAD. These data are consistent with NAM having a mechanism of a ction as a radiosensitiser at least in part by DNA repair inhibition. In addition, it should also be considered that high doses of NAM might cause considerable complications to normal tissue in tumour-bearing i ndividuals.