Low doses of ionizing radiation induce nuclear activity in human tumour cell lines which catalyses homologous double-strand recombination

Abstract

Activity catalysing double-strand DNA recombination has been investigated in human tumour cell lines using an in vitro assay in which nuclear extracts from tumour cells are used to catalyse homologous recombination between deletion plasmids. The cell lines investigated showed comparable constitutive levels of recombination activity. In several cell lines a two- fold to fourfold increase in the frequency of double-strand recombinational events catalysed by nuclear extracts was observed if the cells were exposed to low doses of ionizing radiation. The response was greatest for cells harvested at 6 h after radiation exposure, and the dose to produce an optimal effect was 25 cGy. Cell lines showing this response included a relatively radioresistant human colon cancer line and two cis-DDP (cis-diamminedichloroplatinum II) resistant ovarian tumour cell lines which are cross-resistant to radiation. Sub-lethal doses of cis-DDP were also effective in inducing upregulation of recombinational activity in the cis-DDP resistant cell lines. No change in recombinational activity was seen for radiation/drug-sensitive ovarian cell line following exposure to low drug or radiation doses. These findings are of particular interest since they involve a radiation-induced process with potential for direct involvement in DNA repair. Further studies will be aimed at determining if the extent of resistance to cytotoxic agents is causally related to the degree of inducible recombination activity.

Perspectives on the adaptive response from studies on the response to low radiation doses (or to cisplatin) in mammalian cells

“…and consequently hypothesize that DNA repair must be the factor(s) turned on. 4,17 There is some evidence for this idea, 18,19 which would require protein synthesis, and indeed inhibitors do prevent IRR priming. 6,9,10 Or, rather than extent of repair, perhaps ®delity of repair, is improved.…”