Inhibition of ornithine decarboxylase induction by psoralen plus near ultraviolet light in human cells: the role of monoadducts vs DNA crosslinks

Treatment of plateau-phase human breast carcinoma cells with 4,5',8-trimethyl psoralen (TMP)-plus-near UV light (PUVA) inhibited the transcriptionally-controlled induction of ornithine decarboxylase (ODC). The fluence response curve had a shoulder (Dsub(q) = 560 J m-2) followed by an exponential decline (D0 = 690 J m-2). The cells could not recover from a PUVA dose that inhibited ODC induction by 50% or more. This is consistent with the lack of removal of TMP monoadducts and DNA crosslinks following a similar dose. However, removal of labeled TMP and DNA crosslinks was observed after lower doses during a 24 h period. Using the two-dose approach it was shown that crosslinks are more efficient than TMP monoadducts in inhibiting ODC induction. The same phenomenon was also found with regard to inhibition of RNA synthesis. (author)