We have carried out a study of large malignant skin tumors (squamous cell carcinomas) and other lesions in hairless mice (groups of 38-45) intermittently exposed to ultraviolet light over a period of 15 weeks, beginning when the mice were about 10 weeks old. The several groups were given a standard diet with 0%, 0.3%, 5%, and 10% added L-ascorbic acid (vitamin C) throughout the study. No lesions developed in unirradiated control groups. The lesions were counted every 14 days for 4 months, beginning 4 weeks before the end ofthe period ofirradiation. The observed incidence of lesions of several sizes during successive time periods was analyzed by the statistical method recommended by a committee of the International Agency for Research on Cancer. A pronounced effect of vitamin C in decreasing the incidence and delaying the onset of the malignant lesions was observed with high statistical significance.Interest in vitamin C and other dietary factors in relation to the incidence of and mortality from cancer in human beings has been stimulated by the studies of the value of vitamin C for patients with advanced cancer in Vale of Leven Hospital (Loch Lomondside, Scotland) from 1971 on (1-9). In 1973 it was suggested to one of us (L.P.) that we carry on studies of vitamin C in relation to cancer in animals (8). We began these studies in 1976, and we recently published a report on four studies of vitamin C and vitamin E in relation to skin cancer in hairless mice exposed to ultraviolet light in a standard way (10). In the present paper we report on another study on irradiated mice.About 10 years ago, Homer Black and his collaborators reported that cholesterol-5d,6d-epoxide (cholestan-5d,6d-epoxy-3-ol), a carcinogenic sterol, is formed in skin on ultraviolet irradiation, both in humans (11) and in mice (12, 13). They also reported that dietary anti-oxidants [a mixture ofL-ascorbic acid, butylated hydroxytoluene, D,L-a-tocopheryl acetate (vitamin E), and glutathione] suppressed tumor formation induced in hairless mice by exposure to ultraviolet light (12). Black has given us much information and advice about his techniques. MATERIALS AND METHODSThe hairless mouse is a mutant that loses its hair about 3 weeks after birth, providing easy visibility of skin lesions. It does not have the thymus defect of the nude mutant. Our mice, all females, were of the SK h-hr strain bred at Temple University Health Sciences Center (Philadelphia). They were obtained in March and April of 1980 at age 6-9 weeks. They were maintained for at least 2 weeks on Purina certified rodent chow no.5002 to stabilize the colony before the special diets were begun.They were then distributed five mice to a cage so that the combined weight and mean age per cage were standardized (individual weights, 17.6-32.9 g; ages, 8-11 weeks). Irradiation was begun 10 days later and was continued 5 days per week for about 15 weeks to a total exposure of 135 J/cm2. The radiation was from GE-UA3 mercury arc lamps as described by Black except that an automatic timi...

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A study of the effect of different amounts of L-ascorbic acid (vitamin C), between 0.076% and 8.3%, contained in the food has been carried out with ten groups of RIII mice (seven ascorbic acid and three control groups), with 50 mice in each group. With an increase in the amount of ascorbic acid there is a highly significant decrease in the first-order rate constant for appearance of the first spontaneous mammary tumor after the lag time to detection by palpation. There is also an increase in the lag time. The mean body weight and mean food intake were not significantly different for the seven ascorbic acid groups. Striking differences were observed between the 0.076% ascorbic acid and the control groups (which synthesize the vitamin): smaller food intake, decreased lag time, and increased rate constant of appearance of the first mammary tumor. This comparison cannot be made experimentally for guinea pigs and primates because the control groups would develop scurvy.

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