Loss of expression of basement membrane proteins reflects anomalies of chromosomes 3 and 12 in the rat 4-nitroquinoline-N-oxide model of oral carcinogenesis

Abstract

This study examined the cytogenetic characteristics of keratinocyte cell lines derived from rat oral tissues treated in vivo with the carcinogen 4-nitroquinoline-N-oxide. A parent tumour with a spectrum of differentiation was used to establish clonal subpopulations that formed differentiated (squamous cell carcinomas; SCCs) and undifferentiated (spindle cell phenotype) tumours following transplantation to athymic mice. By contrast to spindle cell tumours, SCCs elaborated basement membrane proteins (laminin and collagen IV). Both diploid and tetraploid subpopulations formed either SCCs or spindle cell tumours. An unbalanced 10q+ translocation was common to all cell lines. Anomalies of chromosomes 3 and 12 (gain, loss, deletions, translocations) were present only in cell lines that formed spindle cell tumours and were absent in keratinocytes forming SCCs. The results suggest that proto-oncogenes and/or tumour suppression genes located to rat chromosomes 3 and 12 may control tumour cell differentiation.