Malignant Transformation of Hamster Embryonic Cells by 4-Hydroxyaminoquinoline N-oxide in Tissue Culture

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Abstract
Hamster embryonic cells were successfully transformed to tumor cells by treatments with 4-hydroxyaminoquinoline N-oxide (4HAQO). This compound is supposed to be an active metabolite of 4-nitroquinoline N-oxide (4NQO). The transformed cells were characterized by randomly oriented arrangement of fusiform cells and their continuous proliferation in vitro over 200 days. Transplantation of these cells gave rise to tumors in newborn and adult hamsters after 56 days in vitro, and finally killed the animals. The tumor was diagnosed histologically as fibrosarcoma. As compared to application of these carcinogens in animals, malignant transformation in vitro was recognized in such a short time as 49 days after the treatment (56 days in total culture days). In untreated cultures, no such transformed cells were found. The controls in the early period of culture revealed a monolayar growth of fibroblastic cells, which was later followed by nonproliferating state of large, flat and granulated cells. The cells of controls failed to grow when inoculated into newborn and adult animals. The experimental system used in this study provides an advantage in that carcinogenic effect of an agent may develop without any appreciable spontaneous cell transformation. Besides 4 HAQO, carcinogens such as 4 NQO and 6-chloro 4 NQO were examined in cultures under the identical conditions. These compounds also effected malignant transformation of hamster embryonic cells.