CARCINOGENESIS 



who discovered these interesting mechanisms. Before examin- 

 ing the evidence which indicates that similar mechanisms 

 are involved in carcinogenesis, it is necessary to emphasize 

 that the development of cancer is far more complex than the 

 transformations observed in the unicellular organisms. A pure 

 strain of cells living under controlled conditions is not subject 

 to the action of antibodies, fibroblasts, leukocytes, hormones, and 

 others factors that help to regulate life in multicellular organ- 

 isms. Thus, it is to be expected that the changes leading to 

 cancer will be complicated and extended because of the moderat- 

 ing influence of the host in combatting deviations from the norm. 

 Despite these complications, it is not premature to examine the 

 biological and biochemical evidence which indicates a similarity 

 in the processes that result in heritable cellular changes in 

 unicellular organisms and in cancer. 



First, there is some indirect evidence that the cause of 

 some cancers is associated with mutations of nuclear genes. 

 Such evidence is based on the findings that nuclear changes are 

 associated with cancer and that carcinogens cause chromosomal 

 aberrations (26), and on the corollary finding that some car- 

 cinogens are mutagenic and some mutagens are carcinogenic 

 (2,29,30,36). 



Second, carcinogenesis may result from deletions of cyto- 

 plasmic factors in a manner analogous to that observed by 

 Ephrussi in yeast transformations (17,18). In the McArdle 

 Memorial Laboratory, James and Elizabeth Miller (44,45) 

 have obtained evidence compatible with this view. They have 

 demonstrated that the carcinogenic amino azo dyes form firm 

 complexes with normally occurring proteins of the liver; but 

 no similar binding was found in hepatic neoplasms. Their 

 results suggest that the carcinogen causes a gradual deletion 

 of certain proteins that are necessary for specialized features of 

 the cell but not for the growth pattern. Similar complexes 

 between proteins of the skin of mice and carcinogenic hydro- 

 carbons have also been demonstrated by E. C. Miller (43) and 

 by Heidelberger (72-74). Of special significance is the fact 



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