RELATION BETWEEN CHROMOSOMAL ALTERATION AND DEVELOPMENT OF TUMORS

Abstract

The present paper deals with karyological studies of tumor cells, with special regard to the relationship between chromosomal alteration and tumor development.(1) In my first karyological study of the Yoshida ascites rat sarcoma (Yosida 1948), I found that the ascites tumor was good material for chromosomal study of tumor cells. In the karyological studies carried out in 1949a and 1949b, the mitotic cells were classified into three types; namely, normal, aberrant and disintegration types. As a result of those studies the normally dividing cells were considered to play an important role in tumor development.(2) Karyotypes in the stemline cells of many tumors in mice and rats deviate from those of normal somatic cells (Tables 1 and 2). The karyotype of stemline lineage, however, is not always stable, but is easily replaced by another cell type, when a more vigorous cell or cells occur in the cell population. Instances of replacement of stemline karyotype in Yoshida rat sarcoma, MY mouse sarcoma, mouse lymphocytic leukemia P388 and mouse hepatomas MH 134 and 129P are given in this paper. Change of stemline karyotypes is accerelated when the tumor encounters an unusual hostile condition. Remarkable change of stemline karyotype was observed in drug resistant P388 in vitro lines, which developed after treatment with 8-azaguanine and amethopterin. In mouse ascites leukemia L-1210, karyotypes in all five drug resistant sublines were also different from that of the sensitive line. From the above several investigations, it can be concluded that chromosome alteration is important and might be a causative process in creating more vigorons cell types.(3) From the karyological studies in various stages of tumor development, it is assumed that normal somatic cells may be converted to tumor cells by following four development stages: (i) Normal development (ND) stage, (ii) Mutant producing (MP) stage, (iii) Mutant selection (MS) stage, and (iv) Tumor development (TD) stage. Among mutant cells, genes favoring acceleration of cell division may be accumulated and finally, the cells they develop into malignant cells having the character of autonomous multiplication (Fig. 7).(4) Tumors produced by tumor virus had mainly normal diploid karyotype. For the induction of tumors by virus a different mechanism from that described above should be considered.