Xeroderma pigmentosum patients, in addition to ultraviolet-induced
skin cancers, have an increased prevalence of
neoplasms occurring in sites shielded from ultraviolet radiation. We postulated that these internal
neoplasms might be related to ingestion of dietary
carcinogens. As model dietary
carcinogens, we studied the
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). These dietary compounds bind to
DNA and are highly mutagenic and carcinogenic. Cytotoxicity of these compounds was examined in cultured lymphoblastoid cell lines from
xeroderma pigmentosum patients in complementation groups A, B, C, D and E and the variant form and from normal donors. All
xeroderma pigmentosum lymphoblastoid cell lines showed a greater reduction in viable cell concentration than the 2 normal lymphoblastoid cell lines following addition of
Trp-P-1 or
Trp-P-2 (5 micrograms/ml) to the culture medium. Possible differences in cellular activation of these compounds were overcome by treating the cells with rat-liver microsome-activated
Trp-P-2. There was a greater reduction in viable cell concentration in the
xeroderma pigmentosum group A and D cells than in the normal lymphoblastoid cell lines
after treatment with activated
Trp-P-2. These data suggest that the
xeroderma pigmentosum DNA-repair system is defective in repairing
Trp-P-1 and
Trp-P-2 induced DNA damage in addition to being defective in repairing ultraviolet-induced DNA damage. Thus
xeroderma pigmentosum patients may be at increased risk of toxicity from some dietary
carcinogens.