The Nature of Organ Specificity in Chemical Carcinogenesis

Abstract

One of the most central problems in human oncology, as well as in experimental carcinogenesis, is that of organ specificity. The most cursory inspection of human cancer morbidity tables (1) shows that not all tissues of man are equally at risk for neoplasia, and that for a given tissue, risk varies with age, sex, and genetic background (Table 1). Where a specific causative agent is known, characteristically it is linked with a relatively narrow spectrum of diseases, or even with a single clinical entity: 2-aminonaphthalene causes carcinoma of the urinary bladder (2); bis (2-chloromethyl) ether (BCME) causes oat-cell carcinoma of the lung (3); vinyl chloride induces hepatic angiosarcoma (4). Major determinants of organ specificity can be found in some cases in peculiarities of metabolism and excretion of the carcinogen, as in the case of the aromatic amines and the urinary bladder; or in a crude biological form of the chemical Law of Mass Action, that the site of highest local concentration is the most vulnerable, as with pulmonary carcinogenesis in those who inhale the volatile, highly reactive BCME. But neither consideration clearly explains why vinyl chloride, when inhaled, selectively induces tumors of the hepatic endothelium while sparing hepatocytes, in which it is presumably metabolized.