Increased chromosome breakage by N-methyl-N1-nitro-N-nitrosoguanidine in patients with adenomatous polyposis coli.

In a search for hypersensitivity to chromosome breaking agents, lymphocytes and fibroblasts from patients with the precancerous condition adenomatous polyposis coli (APC) were treated with N-methyl-N1-nitro-N-nitrosoguanidine (MNNG) and bleomycin. The APC cells showed a significantly increased level of chromatid-type damage following MNNG treatment (5 micrograms/ml for lymphocytes, 1 or 2 micrograms/ml for fibroblasts). No such differential effect was noted for bleomycin, but a threefold increase in "pulverized" cells was seen in APC lymphocyte cultures treated in G0, that is before cells have entered the cell cycle. Increased spontaneous and induced chromosome instability appears to be an important effect of the APC mutant gene as molecular evidence suggests that chromosomal mechanisms are likely to play a major role in tumorigenesis both in this condition and in sporadic colorectal cancer.