Age-related susceptibility of chemical carcinogenesis in BALB/c mice

Age-related declines in physiological functions likely put older subjects at increased risk for tumorigenesis. But the relationship between carcinogenesis and age is still an open question. Recent data also showed that several age-associated immunological parameters are well preserved in the very oldest population, or centenarians. Using 7,12-dimethylbenz[a]anthracene as the tumor-initiating agent and refined croton oil as the promoter, we analyzed the correlation of tumorigenesis and age by two-stage skin tumorigenesis model in BALB/c mice, and detected urine 8-hydroxy-2'-deoxyguanosine and T cell subsets in spleen. The percentages of tumor-bearing mice in 1-,10- and 24-month-old groups were 40% (4/10), 100% (10/10), and 10% (1/10), respectively. After carcinogenesis, mouse urine 8-hydroxy-2'-deoxyguanosine level increased and the percentages of CD4(+), CD8(+), and CD28(+) cells in splenocytes decreased. All mice in this study survived until the end of the 12 weeks. By the tested protocol and doses, our results suggest that a nonlinear correlation exists between tumor incidence and age. The middle-aged mice were most susceptible to chemical carcinogenesis compared to other two groups. Oxidative DNA damage, blood supply, and reduced CD4(+) and CD28(+) T-cell subsets as well as other factors will contribute to such a pattern of chemical carcinogenesis with age.