BIOCHEMICAL PARAMETERS OF EPIDERMAL AGING IN THE HAIRLESS MOUSE AND THE RELATIONSHIP TO UV-CARCINOGENESIS

Epidemiological studies suggest that the incidence of cancer increases with age in both human and animal populations and that declining physiologic condition associated with aging might be responsible. Experimentally, the reverse has been most often observed, that is, older animals appear less susceptible to the induction of UV-carcinogenesis. Thus, we examined several biochemical parameters of epidermal macromolecular synthesis in hairless mice in an effort to gain insight into the role these processes play in physiological aging and their relationship to carcinogenesis. SKh-Hr-1 hairless mice were randomized into two groups (UV-irradiated and non-irradiated controls) and were two months of age at the start of irradiation and biochemical analyses. The UV group received 0.028 sunburn units (SBUs) daily (5 days wk-1) for 16 months from 40 watt BZS-WLG lamps. Stratum corneum turnover rates (SCR), cell label index (CLI), protein, DNA and RNA synthesis, and ornithine decarboxylase (ODC) induction were determined at monthly intervals over a period of two years. There were no age-related tendencies observed in SCR. CLI increased with age. Chronic, low-dose UV had no effect upon either of these parameters. Epidermal capacity for DNA and protein synthesis increased with age from 2 months to 12-15 months at which time both parameters peaked and then began to decline. UV significantly reduced (P<0.04) the magnitude of DNA synthetic capacity at peak periods of synthesis but had no effect upon protein synthesis. RNA synthetic rates declined with age, reaching their lowest levels at 24 months. Further, a significant reduction (P<0.001) in ODC inducibility occurred with advancing age. Comparison of these data with UV-carcinogenesis studies indicates that macromolecular synthetic rates, i.e., DNA and protein, are lowest at times when mice are most susceptible to UV-induced carcinogenesis. Induced ODC activity, believed to be a marker of tumor promotion, was lowest at ages when mice were most refractory to induction of UV-carcinogenesis. Whereas these data provide some insight into the physiologic status of aging epidermis in the hairless mouse, the relationship to UV-carcinogenesis remains speculative.