LOSS OF EXPRESSION OF BASEMENT-MEMBRANE PROTEINS REFLECTS ANOMALIES OF CHROMOSOME-3 AND CHROMOSOME-12 IN THE RAT 4-NITROQUINOLINE-N-OXIDE MODEL OF ORAL CARCINOGENESIS

This study examined the cytogenetic characteristics of keratinocyte ce ll lines derived from rat oral tissues treated in vivo with the carcin ogen 4-nitroquinoline-N-oxide. A parent tumour with a spectrum of diff erentiation was used to establish clonal subpopulations that formed di fferentiated (squamous cell carcinomas; SCCs) and undifferentiated (sp indle cell phenotype) tumours following transplantation to athymic mic e. By contrast to spindle cell tumours, SCCs elaborated basement membr ane proteins (laminin and collagen IV). Both diploid and tetraploid su bpopulations formed either SCCs or spindle cell tumours. An unbalanced 10q(+) translocation was common to all cell lines. Anomalies of chrom osomes 3 and 12 (gain, loss, deletions, translocations) were present o nly in cell lines that formed spindle cell tumours and were absent in keratinocytes forming SCCs. The results suggest that proto-oncogenes a nd/or tumour suppression genes located to rat chromosomes 3 and 12 may control tumour cell differentiation.