Ultrastructural studies on the effect of photoactivated 8-methoxy psoralen. Nuclear changes in a human epithelial...

An established human epithelial cell line was exposed to photoactivated 8-methyoxy psoralen (PUVA); the cells were fixed and processed for electron microscopy 2 hours, 3 days and 6 days thereafter, and the nuclear morphology compared to controls. In the light microscope the cells fixed 3 and 6 days after PUVA exposure showed an increase in the number of multinucleated cells. At the ultrastructural level an increased number of cells with nuclear indentations, cytoplasmic invaginations, pseudoinclusions, nuclear bodies and multiple nucleoli were seen. An increased number of perichromatin granules per cell section and a decrease in heterochromatin situated marginally were observed. In cells from 6 day-old cultures 15 out of 50 nuclei were seen divided into 3-12 nuclear elements, compared with none in the controls. The smaller of these elements tended to be heterochromatic and the larger euchromatic. Generally the nuclear elements were smooth in outline, but elements of bizarre shape were also seen. These consisted of nuclear fragments united by heterochromatic extensions of uniform diameter. When comparing the morphology of PUVA exposed cells with the morphology of non-malignant and malignant cell lines, the PUVA exposed cells appeared to show an increase in morphological markers corresponding to those determined in malignant cells. The possibility that PUVA therapy may cause cancerous transformation is discussed.