© 1983 Oxford University Press
research-article |
Distribution of the carcinogenic tryptophan pyrolysis product Trp-P-1 in control, 9-hydroxyellipticine and ß-naphthoflavone pretreated mice
Department of Pharmacology, SLU, Uppsala Biomedical Centre Box 573, S-75 1 23 Uppsala Sweeden
1Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital F-69, S-141 86 Huddinge, Sweden
Autoradiograms obtained 1–4 h after i.v. injection of the 14C-labelled carcinogenic tryptophan pyrolysis product Trp-P-1 to albino and pigmented mice showed a pronounced uptake of radioactivity in the lymphatic system (thymus, lymphnodes, bone marrow and spleen), in the endocrine system (hypophysis, thyroid, adrenal medulla) and in the liver, kidney medulla and brain. High radioactivity was present in the excretory pathways, predominantly in the bile/intestinal contents. At longer post-injection times (24 h to 6 days) most of the labelled substance had left the tissues, except for the liver which still retained a high concentration of radioactivity. Trp-P-1 is known to be activated by cytochrome P-448. The uptake of radioactivity in the liver could be reduced by pretreatment with the cylochrome P448 inhibitor 9-hydroxy-ellipticine suggesting that the observed accumulation of radioactivity in the liver was partly due to metabolites of Trp-P-1. After pretreatment with the cytochrome P-448 inducer ß-naphthoflavone, the administration of Trp-P-1 resulted in a highly selective accumulation of radioactivity in the lung parenchyma, exceeding all other tissues in the body. ß-Naphthoflavone pretreatment also increased the uptake of radioactivity in the kidney cortex and small intestinal mucosa. As indicated by a high labelling of the pigmented tissues of the maternal and fetal eye, the carcinogen and/or its metabolites were accumulated in melanin.