Preneoplastic lesions as end points in Carcinogenicity testing. II. Preneoplasia in various non-hepatic tissues

The evaluation of the carcinogenic risk deriving from chemical compounds depends mainly on conventional histopathology up to the present. The accepted end point in carcinogenicity testing is the tumor as defined histologically. A great disadvantage of this approach is the long lag period in the development of tumors induced by chemicals. In order to overcome this drawback, many efforts have been made to detect early biological or morphological lesions which might be specific for carcinogens. A great number of short-term tests carried out in vitro provided valuable information about the reactions of cellular constituents and biological macromolecules to the chemicals tested, but they did not allow an unequivocal prediction of the carcinogenic potential of the respective compounds in whole animals, not to mention man. The introduction of modern micromorphological methods such as electron microscopy and cytochemistry in the evaluation of whole-animal studies also revealed many new aspects on carcinogen-induced cellular and subcellular alterations which appeared to be unreliable as indicators of the carcinogenic risk of chemicals. However, during the past two decades a number of characteristic cellular changes has been detected in various tissues, especially in the liver. These changes regularly precede the development of certain tumor types, and are regarded as preneoplastic lesions (1,2). The altered cell populations usually form well-defined foci. They appear prior to the development of tumors in the target tissue of the carcinogen, and should be duly considered in the evaluation of the carcinogenic risk from chemicals in bioassays.