CHEMICAL CARCINOGENESIS

The foregoing proposal is submitted in explanation of the mechanism underlying chemical carcinogenesis. As a first event the initiator induces rare recessive mutations in any of the probably numerous genes which collectively control the regulation of normal cell division. In diploid mammalian cells the mutations would remain unexpressed and the cells harbouring them could persist indefinitely and unrecognisably in the tissue in which they arose. If later a second chemical (the promoter) having the effect of allowing the mutant genes to become homozygous was applied to the tissue, their mutant activity would be expressed to give cells with altered regulation of division resulting in neoplasia. Mechanisms which could lead to homozygosity are discussed. Misdivision, to give duplication of a chromosome bearing a mutant gene and exclusion of its normal homologue, would allow expression of all recessive characters determined by the duplicate thereby permitting the neoplastic cells to show new properties, in addition to altered regulation of division, which formerly were masked in the heterozygous diploid progenitor cells. Oncogenic viruses may similarly affect growth regulating genes by specifically complexing with them or with regions of chromosome in which they are included. A specificity determined by base sequence complementarity of viral and host DNA could result in inactivation of both of a pair of alleles with high frequency and so permit the early expression of virus induced tumours. These would be expected to show a general similarity in contrast to the diversity of tumour types arising from chemical carcinogenesis. © 1969, The British Empire Cancer Campaign for Research. All rights reserved.