Neoplastic response of mouse tissues during perinatal age periods and its significance in chemical carcinogenesis

Abstract

A series of studies pertaining to perinatal carcinogenesis have been reviewed. Their main objective was development and definition of a sensitivity biologic model for carcinogenicity screening. Data were summarized on factors modifying the carcinogenic response of various tissues following transplacental, neonatal-infant, or adult exposure of (B57BL/6J X C3HeB/FeJ)F1 mice to a single administration of ENU. In addition, tumor response of mice treated during specific perinatal age periods with DEN, BP, aflatoxin B1, benzidine . 2HCl, DDT, dieldrin, and safrole were analyzed. The results revealed that the age of the animals at the time of carcinogenic exposure has been the most effective modulator of carcinogenesis in liver, lung, stomach, ovary, and lymphoreticular tissues. Infancy proved to be the most susceptible period to carcinogenesis as demonstrated by a great variety of tissues that responded to treatment and the incidence of tumors which developed. Depending on the nature of carcinogen, variation in organ sites undergoing carcinogenesis was considerable, apparently due to difference in their enzymatic competence to activate and metabolize the agent. Thus a single treatment with ENU, a spontaneously activated type of procarcinogen, induced 59 primary types of tumors in 22 tissues. In contrast, treatment of infants by procarcinogens requiring enzymatic activation led to development of tumors only at a limited number of tissue sites. However, regardless of the type of carcinogen used, the liver consistently responded with development of tumors. Detailed morphologic and biologic evaluations of the induced liver tumors demonstrated in addition to the benign neoplastic variety, the presence of the frank malignant tumors. The character of tumors was dependent not only on carcinogenicity of the agent used but also on the age of mice at the time of carcinogenic treatment. Perinatally induced primary liver tumors showed greater tendency to metastasize and were more readily transplantable into an isogeneic host than those induced at later age periods. Data showed the advantage of prenatal and/or postnatal treatment in combination of life-long exposures to test agents as a more sensitive bioassay system in comparison with solely postweaning treatment. Because the early age period is the most sensitivity life phase to carcinogenesis, it appears to be a good model for prescreening various potential carcinogens, especially when only small amounts of test substances are available. The importance of the proper relationship of such bioassay to the other test systems regarding assessment of potential human risk has been emphasized.