ABNORMAL SENSITIVITY OF SKIN FIBROBLASTS FROM FAMILIAL POLYPOSIS PATIENTS TO DNA ALKYLATING-AGENTS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (4) , 1249-1254
Abstract
Fibroblast cell strains derived from patients afflicted with genetic diseases predisposing to the development of intestinal polyposis and cancer were tested for their sensitivity to the lethal effects of the DNA alkylating agents methyl methanesulfonate (MMS), ethyl methanesulfonate, N-methyl-N''-nitro-N-nitrosoguanidine and 4-nitroquinoline 1-oxide. The genetic syndromes studied were adenomatosis of the colon and rectum, an autosomal dominant trait; Turcot''s syndrome, a rare autosomal recessive polyposis syndrome characterized by CNS tumors; and Gardner''s syndrome, an autosomal dominant syndrome which, in addition to intestinal polyposis, is clinically characterized by osteomas and soft tissue tumors. Survival (relative clone-forming ability) of the various polyposis fibroblast strains was compared to the average survival of 3 normal human fibroblast strains; t test analysis was used of the respective values for the inverse of the slope of the survival curve (DO) and the concentration resulting in 10% survival (D10). Fibroblasts from the patient with adenomatosis of the colon and rectum (strain GM2355) were moderately but significantly sensitive to 4-nitroquinoline 1-oxide. Strain GM2355 was significantly more sensitive to ethyl methanesulfonate based on D10 comparison only. Fibroblasts from the patient with Turcot''s syndrome were hypersensitive to MMS. Fibroblasts from the Gardner''s syndrome proband were moderately sensitive to MMS, ethyl methanesulfonate, and N-methyl-N''-nitro-N-nitrosoguanidine. Fibroblasts from the clinically affected Gardner''s syndrome daughter of the proband were significantly more sensitive to MMS treatment. This differential sensitivity to the DNA alkylating agents suggests that different mechanisms of hypersensitivity to these chemicals may be associated with fibroblasts from the various forms of familial polyposis. [Genetic predisposition to various forms of cancer might be related to a DNA repair defect in human cells.].

This publication has 1 reference indexed in Scilit: