CARCINOGENESIS 



A. GLUCKSMANNt 

 Strangeivays Research Laboratory, Cambridge, England 



The first case of X-ray cancer in man was reported just sixty years ago 

 (Frieben, 1902) and eight years later experimental proof of the carcinogenic 

 action of external radiation was provided by Marie et al. (1910). The short 

 interval between incidental observation and experimental proof contrasts 

 strongly with the long interval between the description of the chimney sweep 

 cancers by Pott in 1775 and the first experimental induction of animal tumours 

 by chemical agents by Yamagiwa and Ishikawa in 1914. Similarly the obser- 

 vation of bone tumours in dial painters after ingestion of radioactive com- 

 pounds (Martland, 1931) was followed quickly by the experimental produc- 

 tion of osteosarcomas in rabbits injected with radium and mesothorium 

 (Sabin et al, 1932). Finally the carcinogenic effect of small doses of whole- 

 body radiation was discovered experimentally (Krebs et al., 1930) before 

 similar experiences in man due to the explosion of the first atomic bombs. 

 For all three main forms of carcinogenic action of radiation experimentation 

 has followed quickly, or even preceded, the observation of clinical cases. 

 Nevertheless the assessment of the carcinogenic risk of radiation still presents 

 difficulties. 



For the induction of cancers by localized external or internal radiation 

 fairly large doses are required, while doses as low as 50 r given to the whole- 

 body of mice are sufficient to induce ovarian tumours in 70% of the animals 

 (Deringer et al, 1955). The carcinogenic risk varies not only with the total 

 dose, but with time and dose fractionation, with the type of organ and 

 volume of tissue exposed, and with the species and strain of animal. For 

 whole-body radiation the role of hormonal mediation and of other systemic 

 factors suggest an "indirect" action of radiation. Thus oestradiol injection 

 into irradiated mice prevents (Gardner, 1950), while the testosterone injection 

 promotes formation of ovarian tumours (Gardner, 1950, 1953). If only one 

 ovary is irradiated, tumours do not develop as long as the other ovary 

 functions, but develop when the functioning ovary is removed (Lick et al, 

 1949). Irradiated ovaries grafted into spayed or irradiated mice produced 

 tumours, but failed to do so in untreated females with functioning ovaries 

 (Kaplan, 1950). On the other hand, unirradiated ovaries grafted into irradiated 

 mice failed to produce tumours. Thus direct and systemic effects are necessary 



t Supported by a grant from the British Empire Cancer Campaign. 



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