Spontaneous in vitro malignant transformation in a xeroderma pigmentosum fibroblast line

This paper deals with a spontaneous malignant transformation in one of our XP fibroblast lines. This cell line, designated XP29MA, was derived from a 14-year-old boy who did not show skin tumors or precancerous alterations either at the time of clinical examination or when the biopsy was taken. We have compared the following features in both the malignant and the benign cell line from which the malignant line developed: tumor formation in nude mice, repair capacity, cytogenetic status, light and electron microscopic characteristics. The benign cell line XP29MA had a doubling time of 4.3 d, did not form tumors in nude mice, showed a very low repair capacity (as determined by colony-forming ability, unscheduled DNA synthesis and alkaline elution) but exhibited a normal cytogenetic and ultrastructural status. In contrast, the transformed cell line XP29MAmal grew three times faster, formed colonies in methyl cellulose, gave rise to fibrosarcomas in nude mice, showed a drastically higher repair capacity, and was characterized by an extreme genetic imbalance, resulting from numerical and structural chromosome alterations of Nos. 1, 3, 4, 8, 12, 16, 17, 18, 20 and 21. Ultrastructural examination revealed fusiform and polygonal cells, the latter exhibiting large indented nuclei, vesicular dilatations of the endoplasmatic reticulum and numerous lysosomes. The higher repair capacity in XP29MAmal cells is tentatively explained in terms of reversion, enhancement of post-replication repair and/or expression of SOS-type functions.