Proliferative response patterns of human fibroblasts after photoinjury with 4,5',8-trimethylpsoralen

The extent of growth suppression and recovery following exposure to 4,5',8-trimethylpsoralen (TMP) plus UV-A irradiation was studied in 3 diploid human fibroblast strains. Inhibition of cellular proliferation was dose-dependent within the concentration range of TMP that was tested (1-4 x 10^-7M), using a constant level of UV-A (0.24J/cm²). The population generation (doubling) times for all cell strains were progressively lengthened under these conditions while maximal cell densities were reduced. At 2-4 x 10^-7M TMP in the presence of UV-A, there was a triphasic pattern of growth which consisted of (1) proliferative activity during the first 24-36 hr, followed by (2) complete growth inhibition for variable periods of time and (3) a recovery period of log phase proliferation that was not as vigorous as measured for untreated cells. There were also declines in the percentage of cells labeled with ³H-Tdr at various times after TMP-UV-A treatment. These measurements were essentially identical for the three fibroblast strains evaluated. In that the cells employed for these investigations were derived from embryonic pulmonary tissue, neonatal foreskin and the buttock skin of an adult male, it seems unlikely that donor age and tissue source were important variables in determining growth response patterns after TMP-UV-A exposure. Because proliferative recovery was attenuated after this photochemical injury, we conclude that the biologic effect(s) of TMP-UV-A extend beyond the known period of psoralen-DNA cross-link removal.