Carcinogenic tryptophan pyrolysis products in human lens

Mutagenic and carcinogenic tryptophan pyrolysis products, 3-amino-1,4-dimethyl-5H-pyrido-[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), have been identified in human cataractous lenses, but not in young bovine lenses. The amounts of Trp-P-1 and Trp-P-2 in senile cataractous lenses were 156.34 +/- 35.63 fmol (mean +/- S.D., n = 10) and 128.27 +/- 40.45 fmol (n = 10), respectively, while those of Trp-P-1 and Trp-P-2 in diabetic cataractous lenses were 158.29 +/- 40.06 fmol (n = 10) and 150.34 +/- 23.77 fmol (n = 10), respectively. In both senile and diabetic cataractous lenses, the concentrations of Trp-P-1 and Trp-P-2 in the insoluble protein fraction (fmol mg-1 protein) were significantly higher than those in the water-soluble protein fraction. Moreover, proteinase-K treatment of lens protein before extraction with methylene chloride significantly increased the recoveries of Trp-P-1 and Trp-P-2. These results clearly indicate that carcinogenic tryptophan pyrolysis products, gamma-carboline derivatives, are present in human cataractous lenses and that these fluorescent carcinogens are significantly concentrated in the insoluble lens proteins.