methylnitronitrosoguanidine and Muscular-Dystrophies

The colony-forming ability of 10 normal human fibroblast cell strains and of 10 strains representing 3 degenerative diseases of either nerve or muscle cells was determined after exposure of the cells to X-rays or beta-particles from tritiated water. Both methods of irradiation yielded similar comparative results. The fibroblast strains from the 5 Usher's syndrome patients and from 1 of the 2 Huntington's disease patients were hypersensitive to radiation, while those from the 3 Duchenne muscular dystrophy patients and the second Huntington's disease patient had normal sensitivity to radiation. These results indicate both disease-specific and strain-specific differences in the survival of fibroblasts after exposure to ionizing radiation.

Topics: Cell Survival; Fibroblasts; Humans; Huntington Disease; Methylnitronitrosoguanidine; Muscular Dystrophies; Neuromuscular Diseases; Reference Values; Syndrome; Tritium; X-Rays

Lymphoblastoid lines from nine Usher's syndrome (recessively inherited retinitis pigmentosa and congenital sensorineural deafness) patients (representing eight kindreds) and from ten Duchenne muscular dystrophy patients (representing seven kindreds) showed a small but statistically significant hypersensitivity to the lethal effects of X-rays, as measured by the cellular ability to exclude the vital dye trypan blue, when compared with lines from 26 normal control subjects. Fibroblast lines from the Usher's syndrome patients, treated with X-rays or the radiomimetic, DNA-damaging chemical N-methyl-N'-nitro-N-nitrosoguanidine, also showed a statistically significant hypersensitivity when compared to normal fibroblast lines. These findings are consistent with the possibility that defective DNA repair mechanisms may be involved in the pathogenesis of these degenerative diseases.

Topics: Adolescent; Adult; Aged; Ataxia Telangiectasia; Cell Line; Cell Survival; Child; Child, Preschool; Deafness; DNA Repair; Female; Fibroblasts; Humans; Infant, Newborn; Lymphocytes; Male; Methylnitronitrosoguanidine; Middle Aged; Muscular Dystrophies; Nerve Degeneration; Retinitis Pigmentosa

Statistical methods are presented for estimating and comparing survival curves obtained from experiments in which cells are exposed in vitro to increasing doses of a DNA-damaging agent. These methods, which are applicable in a variety of cell survival assays, are illustrated in the evaluation of two sets of experiments in which the colony-forming ability of fibroblast cell lines from 9 muscular dystrophy patients and 17 normal individuals were studied after exposure to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).

Topics: Cell Survival; Colony-Forming Units Assay; Fibroblasts; Humans; In Vitro Techniques; Mathematics; Methods; Methylnitronitrosoguanidine; Models, Biological; Muscular Dystrophies; Statistics as Topic