Methionine dependence in skin fibroblasts of humans affected with familial colon cancer or Gardner's syndrome.

Reduced growth in methionine-deficient, homocysteine-, folic acid-, and vitamin B12-supplemented medium, a characteristic of tumor and transformed cell lines, was investigated in skin fibroblasts of patients affected with hereditary colon neoplasms. The presence or absence of this phenotype was studied in 37 cell lines from either low-risk subjects or members of families with Gardner's syndrome (GS) or familial colon cancer (FCC). Growth constants of skin fibroblasts of the low-risk group were not significantly different in the presence of methionine (Kme) or absence of methionine (Kho) (0.106 +/- 0.011 and 0.098 +/- 0.011, respectively). However, growth constants of skin fibroblasts of both GS and FCC were significantly reduced in the absence of methionine. In GS, Kho = 0.086 +/- 0.006 and Kme = 0.120 +/- 0.006 (P less than .01). In FCC, Kho = 0.048 +/- 0.007 and Kme = 0.084 +/- 0.009 (P less than .01). Thus the growth of skin fibroblasts from both GS and FCC was methionine dependent. This phenotype was expressed in skin fibroblasts of an individual several years before any clinical manifestation of GS. In all populations studied the phenotype was independent of the age or sex of the individuals, aging of the cell lines, low serum concentration, and acute carcinogen treatment. In addition, there is a significant correlation (r = -0.85, P less than .001) between the disorganization of actin cables of the skin fibroblasts and the ratio of the growth constants. These data constitute the first report demonstrating methionine dependence in cell lines that are not derived from transformed cells, tumor cells, or fetal cells but are derived from skin fibroblasts of patients with hereditary colonic neoplasms. Inasmuch as these cells are not target cells related to colon cancer, the phenotype appears to be the expression of an inherited autosomal dominant genotype related to the oncogenic transformation.