Application of cytogenetic methods to analysis of etiologic factors in carcinogenesis

The study of chromosomal aberrations in tumour cells by means of modern banding techniques has become a rapidly expanding branch of cancer research. Large amounts of information about cancer-associated chromosomal aberrations have accumulated, and new data continue to appear at a rapid rate. The systematic evaluation of these data has disclosed a number of correlations between chromosomal change and neoplastic disease in experimental animals and man: (1) Chromosomal aberrations are strictly non-random, and in several instances the aberrations are highly consistent and show a remarkable degree of specificity. (2) Chromosomes selectively involved in different types of neoplasia cluster to certain specific chromosome types, and evidence has been presented indicating that certain chromosomal regions may be affected selectively. (3) Suggestive results from work with experimental tumours indicate a direct interaction between the tumour-inducing factor and the chromosomes of the host cell. A hypothetical model, originally proposed by Levan and Mitelman (1977) and elaborated in detail by Mitelman and Levan (1981) to explain the role of chromosomal aberrations in malignant development, is presented. According to this idea, the chromosomal aberrations associated with malignancy may be of essentially two distinct kinds, with different modes of origin. One kind of aberration, the primary or active, arises from direct interaction between the inducing agent and the genetic material of the target cell. Primary aberrations are therefore located in specific chromosomal regions. The other kind of aberration, the secondary or passive, arises by chance disturbances of mitosis. Since, however, only those secondary changes that happen to enhance the effect of the primary change have selective value and will thus accumulate in a population, the passive changes exhibit distinct nonrandom patterns that reflect the primary changes. Conversely, it should be possible to deduce from the distribution of aberrations which chromosomes were originally affected by a primary change; and close observation of those chromosomes involved in nonrandom changes should therefore give indications as to the location in the genome of the original lesions induced by the oncogenic agent.