Malignant transformation of a mouse epithelial cell line with poly cyclic aromatic hydrocarbons

Abstract

MALIGNANT transformation of cells in culture can serve as a means for studying cellular and molecular mechanisms of chemical carcinogenesis and as a method for screening for environmental carcinogens (see refs 1, 2 for reviews). Although most of these systems involve fibroblast cultures from mouse, rat and hamster embryos^3–5, there are few reports of the malignant transformation of epithelial cell cultures except with liver cells^6,7. However, there are some inherent difficulties in working with epithelial cells derived from liver, a highly specialised organ with a multitude of enzyme activities. Many of these enzymes tend to decrease in activity in long-term culture, and may not be equivalent biochemically to their state in vivo. Thus, biochemical studies of carcinogenesis are difficult with such cells, and there are no reports of a normal hepatocyte line that can be transformed in culture and produce a hepatoma on inoculation into the syngeneic host. There are some reports of malignant epithelial cell lines that originated from treating primary cultures obtained from urinary bladder, trachea, kidney, prostate and submandibular gland with different chemical carcinogens^8–13. In such cases, however, there are no normal counterparts available for comparison of biological properties. So far as we know, no line of epithelial cells apart from liver cells has transformed with chemical carcinogen and given rise to carcinomas when inoculated in the appropriate host. We now describe an epithelial cell line from wild mouse embryo, which can be transformed with polycyclic aromatic hydrocarbons. These transformed cells produce poorly differentiated carcinomas when inoculated into nude mice.