Is there a diurnal variation in the susceptibility of mouse skin to the tumorigenic action of methylcholanthrene? A study of tumour yield with special reference to the variation between cages.

Skin tumour development was studied in groups of mice painted once with 125 mug of 3-methylcholanthrene (MCA) either at 12:00 or at 24:00 MET. Eight animals were kept in each box. The animals were observed weekly for 20 months and all tumours were registered. There was no difference between the two groups of mice as regards tumour induction time or number of papilloma-bearing mice. In the groups of mice treated at 24:00 the number of skin tumours to develop was 9 per cent higher than in groups of mice treated at 12:00. This difference in papilloma yields is not statistically significant. Among female mice painted at 24:00 carcinoma-bearing animals were significantly more numerous (50 per cent) than among those painted at 12:00, whereas there was no difference between the groups of male mice. Considering the groups collectively (males + females), the intergroup difference (17 per cent) in advantage of painting at 24:00 was barely significant (0.5 less than p less than 0.10). There was no difference between the groups as regards the total number of carcinomas to occur. When the tumour yields in individual boxes were found to vary greatly. The slight increase in tumour yield after night painting correlates with the circadian variation in proliferative activity of the epidermidis. Previous reports in the literature have shown similar differences. Further investigations and better methods seem necessary before a definite conclusion can be drawn concerning a possible diurnal variation in the susceptibility of mouse skin to chemical carcinogenesis. It is also emphasized that it is necessary to exercise great caution when the results of classical epidermal chemical carcinogenesis experiments are to be interpreted. It seems necessary to observe animals for at least 15 months before any conclusion can be drawn.