Skin fibroblasts from patients with the Li-Fraumeni familial cancer syndrome have been reported to show abnormalities in their response to X-irradiation. We have examined the response of fibroblasts from affected and nonaffected individuals in three families to treatment with four DNA-damaging agents: X-rays, UV light, N-methyl-N′-nitro-N-nitrosoguanidine, and mitomycin C. Test cells along with additional cell bank control strains were received coded and blinded. The same strains were studied on 2 or 3 separate occasions; each of these groups was coded differently. The cytotoxic effects of the four agents were examined by a colony formation assay. Sensitivity to the induction of chromosomal aberrations by X-rays was also measured. In all cases, the response of cells from affected individuals did not differ significantly from that of cells from unaffected (not at risk) family members nor of cell bank controls. The response of somatic cells from members of Li-Fraumeni cancer families to DNA-damaging agents does not appear to be a fruitful approach to the detection of at-risk individuals.


Supported by Program Project Grant CA-33624, Research Grants CA-27925, 34936, and 38929 (all to L.C.S.), and Center Grant ES-00002 from the US National Institutes of Health.

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