Attenuation of catalase activity in the malignant phenotype plays a functional role in an in vitro model for tumor progression

We have developed an in vitro model to study the molecular mechanisms of tu mor progression. Using repeated treatments with ionizing radiation or N-met hyl-N'-nitro-N-nitrosoguanidine (MNNG), we caused malignant progression of a papilloma producing mouse keratinocyte cell line, 308 cells. In a previou s study we have shown that the malignant variants of 308 cells have elevate d reactive oxygen species (ROS) levels, and have established a functional r ole for the pro-oxidant state in the progressed phenotype (Carcinogenesis 2 0 (1999) 2063). In this study, we have evaluated the status of intracellula r defense mechanisms for ROS scavenging in the progressed phenotype to iden tify sources that contribute to their pro-oxidant state. Our results demons trate that a reduction in several anti-oxidant defense mechanisms, includin g catalase and glutatl tione S-transferase mu, correlates with the emergenc e of the malignant phenotype. We provide evidence that attenuation of catal ase activity may play a functional role in the malignant progression of mou se keratinocytes. (C) 2001 Elsevier Science Ireland Ltd. All rights reserve d.