[Supertransformation of a human lymphoblastoid cell line by chemical carcinogens].

Abstract

We have studied the in vitro malignant progression of human lymphoid cells by the combined effect of genetic, viral and mutagenic factors. A lymphoblastoid cell line immortalized by Epstein-Barr virus was used; it was derived from a patient suffering from ataxia-telangiectasia, a genetic disease linked to a deficiency in DNA repair. Cells were treated by sub-toxic doses of two potent mutagens (carcinogens), NQO (4-nitroquinolein-oxid) and R 7 000 (2-nitro-7-methoxy-naphto-furan). The treated cells showed an increased ability to form colonies in soft agarose, among which some compact colonies appeared, different from the diffuse colonies formed by untreated control cells. Sub-clones derived from these compact colonies differ also from the original cells by their behavior in liquid culture medium, by their increased tumorigenicity in Nude Mice and by their capacity to form nodules on Chicken chorioallantoic membrane. Some of the sub-clones produce non-regressing large tumors in Nude Mice with a cell inoculum lower than that required for Burkitt lymphoma cells while being less invasive than the latter. However, by their morphology, the malignant cells of the sub-clones remain similar to the original lymphoblastoid cells. Thus, such a malignant progression obtained in vitro cannot be considered as identical to that which leads to Burkitt lymphoma in African children.