INVITRO MODELS OF HUMAN COLORECTAL-CANCER

Epithelial cell lines that differentiate in vitro have been isolated f rom hereditary and sporadic colorectal adenomas representing different stages in tumour progression, from small adenomas with a low malignan t potential to large adenomas with a relatively high malignant potenti al. The majority of cell cultures derived from small adenomas senesced , whereas the larger adenomas were more likely to give rise to an immo rtal cell line. Karyotypic analysis has shown that specific abnormalit ies of chromosomes 1, 6, 7, 13, 14, 17, 18 and 22 occur in these adeno ma cell lines. Abnormalities of chromosome 1 have been implicated in t umour progression and the in vitro immortalization of colorectal adeno mas. Molecular and cellular changes involving abnormalities of chromos omes 1 and 18, TP53 and ras gene mutations and reduced response to the growth inhibitory effects of TGFB and sodium butyrate, which occur du ring tumour progression, suggest that the in vitro model has relevance to in vivo carcinogenesis.