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Gene Elimination in Carcinogenesis: Reinterpretation of the Somatic Mutation Theory¹

Chester Beatty Research Institute, Institute of Cancer Research, Royal Cancer Hospital, London, S.W. 3, England

A study was undertaken in Drosophila of the mutagenic properties of representatives of the various carcinogenic chemical series: alkylating agents, nitroso compounds, hydrocarbons, aromatic amines, and urethan. Mutations arising from direct intramolecular DNA damage, such as point mutations and chromosome breaks leading to viable rearrangements, occurred only with the alkylating agents and the nitroso compounds; urethan and its metabolites were also weakly effective as regards point mutations in mature sperm. A statistical analysis was undertaken for the assessment of whether a rank correlation occurred between the activities of several alkylating agents with respect to the induction of point mutations and pulmonary tumors, but this proved to be insignificant.

All the tested compounds were active in the induction of small chromosome deletions resulting in Minutes, and a suggestive correlation between this function and carcinogenicity seemed to occur both between and within the various chemical series. The induction of these deletions with the hydrocarbons and aromatic amines and, in part at least, even with the alkylating carcinogens, appeared to be indirect; this was probably due to the in situ interference with the reproduction or repair of genic DNA.

¹ This work was supported by grants to the Chester Beatty Research Institute (Institute of Cancer Research, Royal Cancer Hospital) from the Medical Research Council and the British Empire Cancer Campaign for Research, and by Research Grant CA-03188-08 from the National Cancer Institute, USPHS.

Received 1/23/69. Accepted 3/25/69.

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