344 5. M. Siegel and F. Porto 



"faults" is an accelerated process leading to deterioration of 

 structures and functions in nucleus and crytoplasm. Senescent 

 degeneration is then under way. 



7. Attainment of some large acceptor/donor ratio corresponds to 

 major losses in maintenance and synthetic capacities (e.g. fail- 

 ure in protein synthesis) limiting survival of the cell, etc., to the 

 lifetime of residual enzymes and other already formed species. 

 The terminal phase of senescence is in progress. 



8. Antioxidants which promote growth may do so by maintenance 

 of a relatively youthful, reduced state. They enhance cellular 

 abilities to resist oxidant damage. 



9. Increased oxidant stress shifts the role of antioxidants from 

 functions in quantitative growth control to functions in survival 

 on an all-or-none basis. 



10. Under reduced oxidant stress hormonal requirements will be 

 lowered. Growth can be enhanced by increase in antioxidant 

 or decrease in oxidant as long as their ratio lies within suitable 

 limits. Further, maturation processes will be retarded. 



11. Some low value for the acceptor/donor ratio should correspond 

 to the chemically reduced state which favors proliferating 

 cells. Electron mobility is characteristic of most estrogens, 

 androgens, and carcinogens, and addition of such donors must 

 lower the ratio into this critical region. 



ANTIOXIDANT ACTIVITY AND GROWTH 



General Considerations 



The existence of a relationship between reducing agents and 

 growth is established. In animal systems, the thiol-disulfide equilibrium 

 has been implicated in cellular multiplication (1, 19). Thyroxine, a 

 powerful antioxidant (23), is implicated directly in growth processes, 

 possibly by way of its ability to shift the thiol-disulfide equilibrium 

 toward the reduced state (13). Other substances which stimulate tissue 

 growth or regeneration include phenols, polynuclear hydrocarbons, 

 arylamines (10,11), carbazoles, stilbenes, and phenothiazine, and tri- 

 phenylmethane dyes (1, 17, 19). Among these structures a common fea- 

 ture is their high level of electron availability. All of these molecular 

 types contain mobile tt- orbital electrons or coupled ??(nonbonding)- 

 TT - systems if atoms such as N, S, or O are on or in the aromatic system. 



Antioxidant or electron-donor properties may also be found among 

 plant regulators, including indoles, aryloxy compounds, unsaturated 

 hydrocarbon derivatives, coumarins, etc. (19, 23, 26, 27). Among the 

 conventional reducing agents involved in growth processes are ascorbic 

 acid and the thiols. In contrast with the growth-promoting inhibitors 



