Relationship between x-ray exposure and malignant transformation in C3H 10T1/2 cells.

Abstract

The appearance of transformed foci after x-irradiation of the C3H 10T1/2 line of murine cells requires extensive proliferation followed by prolonged incubation under conditions of confluence. When the progeny of irradiated cells are resuspended and plated to determine the number of potential transformed foci, the absolute yield is constant over a wide range of dilutions and is similar to that observed in cultures that have not been resuspended. In addition, for cells exposed to a given x-ray dose, the number of transformed foci per dish is independent of the number of irradiated cells. These observations suggest that few, if any, of the transformed clones occur as a direct consequence of the x-ray exposure and challenge the hypothesis that transformed foci are the clonal products of occasional cells that have experienced an x-ray-induced mutational change. Rather, it appears that at least two steps are involved. We suggest that exposure to x-rays result in a change, for example, the induction or expression of some cell function, in many or all of the cells and that this change is transmitted to the progeny of the surviving cells; a consequence of this change is an enhanced probability of the occurrence of a second step, transformation, when these cells are maintained under conditions of confluence.

Do mitochondrial DNA fragments promote cancer and aging?

“…There they may trigger the induction of DNA repair enzymes, some of which are error prone [72][73][74]. If such repair was sustained for several cell cycles a promutagenic state could be established [5,75,76]. This mechanism (the induction of sustained, errorprone DNA repair) might affect a far greater proportion of the transfected cells than a mechanism requiring the insertion of specific sequences and/or insertion at specific sites.…”

Oncogenic transformation of murine C3H 10T1/2 cells resulting from DNA double-strand breaks induced by a restriction endonuclease

“…the Philadelphia chromosome in chronic myeloid leukaemia) which may be causally related to the transformation process (Klein & Klein, 1984). Oncogenic transformation of cultured cells can be studied in the murine C3H 10T1/ 2 system (Reznikoff et al, 1973;Han & Elkind, 1979;Kennedy et al, 1980). The 10T1/2 system may not be an ideal system as a model for the study of cancer induction in the whole animal.…”

The mysterious steps in carcinogenesis

“…This single treatment with a mutagen apparently causes cells to undergo a permanent change so that, for the rest of the mouse's life, its skin has become susceptible to the production of papillomas and carcinomas on exposure to the non-mutagenic irritants in croton oil. Surprisingly, a similar sequence has been seen using cells in vitro, where brief exposure to X-rays or methylcholanthrene apparently produces a permanent change in every cell so that, many generations later, its descendants occasionally undergo 'spontaneous' transformation into cancer cells (Kennedy et al, 1980(Kennedy et al, , 1984. Why does there have to be a long interval between a cell's exposure to a mutagen and the expression of the resulting mutations, and why do only a minority of the cell's descendants express these mutations?…”