Rapid body weight gain increases the risk of UV radiation-induced skin carcinogenesis in SKH-1 hairless mice

Abstract

Although it is well known that caloric restriction reduces the risk of chronic diseases including cancer, the role of weight gain in the development of UV light-induced tumors has not, to our knowledge, been investigated. In view of the increase in obesity worldwide, we asked the question whether there is any relationship between body weight gain and skin tumor development. We subjected 3 groups, each composed of 30 SKH-1 hairless female mice, to UV radiation (30 mJ/cm(2), twice weekly for 17 weeks) and observed tumor formation over the ensuing 8 to 13 weeks: group 1 received pelleted diet; group 2 received pellets during the irradiation period and was then switched to powder; and group 3 received powder exclusively. At the end of the experiment, the mean body weight of group 1 was 32.1 +/- 0.5 g, whereas that of groups 2 and 3 was 39.0 +/- 1.5 and 39.5 +/- 1.4 g, respectively. Tumor incidence reached 90% at 8 weeks after completion of irradiation for the animals in group 3 and at 13 weeks for the animals in group 2. Similarly, at 8 weeks after irradiation when all animals of group 3 were euthanized, tumor multiplicity was 0.8, 1.2, and 3.2 for groups 1, 2, and 3, respectively. Thus, in comparison with the mice consuming pellets, the powder-fed mice gained weight more rapidly and developed tumors much faster. Considering the escalating numbers of individuals worldwide who are overweight or obese, our findings provide further impetus for advocating healthier diets and maintenance of constant body weight in adults.

Figure 1. SKH-1 hairless mice fed powdered diet gain weight much more rapidly than their counterparts that are fed pelleted diet

Female SKH-1 hairless mice were exposed to UVB radiation (30 mJ/cm²/session) twice a week for 17 weeks. At the onset of the experiment, when the animals were 5- to 6-week-old, they were divided into three groups of 30 each. All were fed AIN-76A diet (n=30 animals per Group). Group 1 (●) was fed pellets for 30 weeks. Group 2 (○) received pellets for 17 weeks and then were switched to powder for 13 weeks, when the experiment was terminated. Group 3 (■) was fed powder for 24 weeks, at which time point all animals from that group were euthanized. Body weights were monitored weekly and are shown as mean values. The arrow indicates the end of the UV irradiation schedule, which was also the time when the animals from Group 2 were switched from pellets to powder. Note that the animals from Group 2 began increasing their body weight as soon as they were changed to the powder. There were significant differences in weekly body weight (P<0.001) as determined by ANOVA, followed by post-hoc Bonferroni recalculation of pairwise significance: (nsd – no significant difference; average weight per mouse); significant differences are indicated by the symbols at the top of the graph: a- 1,2>3; b- 1,2,3 nsd; c- 3>1,2 ; d- 3>2>1; e-3,2>1; f-2>1.

Figure 2. SKH-1 hairless mice fed powder develop UV radiation-induced skin tumors much more rapidly than their counterparts that were fed pellets

SKH-1 hairless mice (n=30 animals per Group) were irradiated with UVB (30 mJ/cm²/session) twice a week for 17 weeks and received AIN-76A diet. During the period of irradiation, Group 1 (●) and Group 2 (○) were fed pellets, whereas Group 3 (■) was fed powder (n=30 for each Group). After completion of irradiation (time 0 on the graphs), the animals from Group 1 (●) remained on pellets, whereas those from Groups 2 (○) and 3 (■) were fed powder. The appearance of tumors was monitored on a weekly basis, and tumors were mapped, counted, their sizes were recorded. (A) Tumor incidence, i.e., percent of mice with tumors within each group; log-rank comparisons for equality between Groups were significant (P<0.0001) for Group 1 v. 3 and Group 2 v. 3, and at P=0.0012 for Group 1 v. 2; (B) Tumor multiplicity, i.e., number of tumors per mouse, expressed as mean values ± SEM, (n=30 animals per Group). (C) Tumor incidence (% mice with tumors) as a function of body weight.