Progression in a chemically induced transplantable human pancreas carcinoma

A methylnitrosourea (MNU)-induced transplantable human pancreas carcinoma was examined, at 3, 12, 18 and 36 months after its development, for growth and invasiveness in nude mice, karyotypic alteration and the evolution of marker chromosomes. Progression in tumorigenicity and invasiveness of cells were evident by a significant increase in tumor diameters produced within 8 weeks by the cells at 36 months as compared to those developed by cells from 3-month-old cell lines. Chromosome analysis at 3 months showed normal 46 XX karyotype in about 80% and minor anomalies in 20% of the cells. At 12, 18 and 36 months, all cells were hyperdiploid with 53-61 chromosomes and several abnormal marker chromosomes. Marker chromosomes showed non-reciprocal translocations, deletions, inversion and isochromosomes. The absence of chromosome 13 from the earlier stage onward may have resulted in the loss of genes which suppress tumorigenicity. The increase in homogeneously staining regions of marker chromosome 3 at later stages appears to parallel the augmentation in tumor growth and mitotic indices.