INCREASED APOPTOSIS DURING PAPILLOMA DEVELOPMENT IN MICE SUSCEPTIBLE TO TUMOR PROGRESSION

Programmed cell death (apoptosis) is known to occur not only during no rmal development and tissue remodeling but also during neoplasia. Desp ite the suggested role of apoptosis in preventing the proliferation of malignant cells, a positive correlation between tumor progression and the presence of apoptotic cells has been found in different types of cancer, including epithelial tumors. In normal mouse skin, the role of apoptosis is not completely understood, and it has been suggested tha t terminal differentiation may be a special case of apoptosis. In the work reported here, we counted apoptotic cells in mouse skin tumors ge nerated with a two-stage chemical carcinogenesis protocol. We analyzed papillomas from outbred SENCAR mice at different times during promoti on, and to better determine the correlation between apoptosis and tumo r progression, we compared papillomas generated from two inbred strain s derived from the SENCAR stock that differ in their susceptibility to tumor progression. Our results showed that in mouse skin chemical car cinogenesis, the number of apoptotic cells was greater in papillomas t hat may have been in the process of progressing to squamous cell carci nomas. This conclusion is also supported by the fact that papillomas f rom SENCAR P/Bt. mice, a tumor progression-susceptible strain derived from outbred SENCAR mice, had more apoptotic cells than papillomas fro m progression-resistant SSIN mice. (C) 1997 Wiley-Liss, Inc.