Genetic analysis of tumerigenesis: XVI. Chromosome changes in azacytidine- and insulin-induced tumorigenesis

Abstract

Chromosome changes accompanying differentiation and tumorigenesis in azacytidine- (azaC) and insulin-induced preadipocytes of the Chinese hamster embryo fibroblast cell line CHEF/18 are described. Karyotype analysis of 47 clones, subclones, and tumor-derived cells has shown that trisomy for chromosome 3q (mar 1) is characteristic of azaC preadipocytes but not of insulin preadipocytes. AzaC preadipocytes were consistently tumorigenic as well as trisomic for chromosome 3q, whereas most insulin preadipocytes were nontumorigenic and diploid. Only the few insulin preadipocytes that were tumorigenic were also trisomic for chromosome 3q. Among the tumor-derived cell lines recovered from azaC preadipocytes injected into nude mice, four had no additional chromosome changes except trisomy for 3q, as detected by karyotype analysis. Thus trisomy for 3q may be a sufficient chromosome change to induce tumor-forming ability in these cells. The rearrangements of chromosome 3 seen in this and other work pinpoint the trisomic region between the centromere and 3q5.

Plasmid-induced "hit-and-run" tumorigenesis in Chinese hamster embryo fibroblast (CHEF) cells.

“…In previous studies with diploid CHEF cells, the occurrence of aberrations has been a consistent property of tumorigenic and tumor-derived cells (19,24,25) but not of transformed cells lacking tumor-forming ability (25). It was inferred from these and other findings that the transformed cells may have undergone single-gene mutations, whereas multiple genetic changes were involved in tumorigenesis.…”

“…In all, 19 foci from pSV2gpt treatment and 8 foci from J132 were grown up, tested, and found to lack detectable plasmid DNA. Seven out of seven J132 lines and 14 out of 19 pSVgpt lines tested in nude mice were tumorigenic, but no plasmid DNA was detected in their tumor-derived cells.…”

“…For tumorigenicity assays, congenitally athymic (nude) BALB/c mice were injected subcutaneously in the flank with 4-10 x 106 cells (3). Chromosomes were prepared for Giemsa-binding analysis as described (19).…”

Effect of cellular determination on oncogenic transformation by chemicals and oncogenes.

“…In this respect, they differ from 5-aza-CR-derived preadipocytes of Chinese hamster embryo fibroblasts, which are tumorigenic (12). Their nontransformed phenotype justifies the use of these cells in experiments to understand the relationship between myogenic determination and susceptibility to transformation.…”

Genetic analysis of tumorigenesis: a conserved region in the human and Chinese hamster genomes contains genetically identified tumor-suppressor genes.

“…Chromosomal analyses of premalignant, tumorigenic, and tumor-derived Chinese hamster cells reported from this (4)(5)(6)(7) and other laboratories (8,9) have identified two cytogenetic events associated with tumor-forming ability in nude mice: trisomy of 3q (the long arm of chromosome 3) and loss of the corresponding 3p (the short arm). These and other observations (R. W. Craig, I. K. Gadi, and R.S., unpublished data) led us to postulate that there might be a tumor-suppressor gene on 3p (7) as well as an oncogene on 3q.…”