A general theory of carcinogenesis.
A GENERAL HYPOTHESIS OF CARCINOGENESIS IS PROPOSED CONSISTING OF THE FOLLOWING FEATURES: (1) It is suggested that all cells possess multiple structural genes (Tr) capable of coding for transforming factors which can release the cell from its normal constraints on growth. (2) In adult cells they are suppressed by diploid pairs of regulatory genes and some of the transforming genes are tissue specific. (3) The Tr loci are temporarily activated at some stage of embryogenesis and possibly during some stage of the cell cycle in adult cells. (4) Spontaneous tumors, or tumors induced by chemicals or radiation, arise as the result of a double mutation of any set of regulatory genes releasing the suppression of the corresponding Tr genes and leading to transformation of the cell. (5) Autosomal dominant hereditary tumors, such as retinoblastoma, are the result of germ-line inheritance of one inactive regulatory gene. Subsequent somatic mutation of the other regulatory gene leads to tumor formation. (6) The Philadelphia chromosome produces inactivation of one regulatory gene by position effect. A somatic mutation of the other leads to chronic myelogenous leukemia. (7) Oncogenic viruses evolved by the extraction of host Tr genes with their conversion to viral transforming genes. As a result, in addition to the above mechanisms, tumors may also be produced by the reintroduction of these genes into susceptible host cells.
D000818:Animals; D002273:Carcinogens; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D004279:DNA, Viral; D004331:Drosophila melanogaster; D005399:Fishes; D005796:Genes; D005799:Genes, Dominant; D005808:Genes, Recessive; D005809:Genes, Regulator; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics; D009153:Mutagens; D009154:Mutation; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D009858:Oncogenic Viruses; D012175:Retinoblastoma / Q000235:genetics; D013696:Temperature
D002273:Carcinogens; D004279:DNA, Viral; D009153:Mutagens