Fragile sites are targets of diverse mutagens and carcinogens

Using a high-resolution chromosome banding technique with cultured human lymphocytes and caffeine as a mutagen enhancer, 16 different mutagens and carcinogens were found to induce 110 recurrent fragile sites. All agents produced chromosome breaks and the majority of the 110 recurrent break sites involved were elicited by at least half of all agents, even though they act through different molecular mechanisms. Two of the agents used are known to induce hypersensitive chromatin sites in regulatory regions of active genes. Of the 110 mutagen-sensitive fragile sites, 50 coincide with the location of 50 of 75 specific cancer chromosome breakpoints (67%) and 21 with the location of 26 of 36 oncogenes (72%). The expression of so many similar fragile sites following exposure of cultured cells to diverse mutagens, and the high correlation of these sites with cancer chromosome breakpoints and oncogenes, suggests that they can be general targets of mutagenic action.