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DIFFERENTIAL sensitivity of normal and neoplastic rodent fibroblasts growing in vitro to the toxic action of carcinogenic polycyclic hydrocarbons, suggested long ago by Haddow (1938), has been demonstrated by a number of investigators (Starikova and Vasiliev, 1962;Berwald and Sachs, 1963; Alfred and collaborators, 1964;Diamond, 1966). Neoplastic cells were found to be much more resistant to these compounds than their normal counterparts. Resistance to the toxic effects of carcinogenic hydrocarbons was shown to be characteristic for the cells of sarcomas induced by various types of agents: carcinogenic chemicals, plastic films, SV40 and polyoma viruses. Thus, decrease of the sensitivity to carcinogens regularly accompanied neoplastic transformation of these cells (see review and discussion in Vasiliev and Guelstein, 1963Guelstein, , 1966.The causes of the differential sensitivity of normal and neoplastic cells to carcinogenic hydrocarbons remain obscure. These compounds undergo various metabolic transformations in vivo (see review in Boyland and Weigert, 1947; Miller and Miller, 1965). In vitro they are rapidly accumulated by normal and neoplastic cells (Marimura, Kotin and Falk, 1964;Alfred et al., 1964;Diamond, 1966). It was not known, however, whether these substances might be metabolized by cells growing in vitro.The experiments described in this paper were performed in order to study the rate of metabolism of a carcinogenic hydrocarbon, 3,4-benzopyrene (BP), in cultures of normal and neoplastic fibroblasts of mice and hamsters.Similar experiments were made with cultures of fibroblasts from normal human embryos. As shown by Diamond (1966) and confirmed in this laboratory, normal human fibroblasts, in contrast to normal rodent cells, are resistant to the toxic effects of carcinogenic hydrocarbons. MATERIALS AND METHODS Cell culturesFirst subcultures of trypsinized cells of mouse, hamster and human embryos were used; the age of human embryos taken for trypsinization was about 2-3 months, that of rodent embryos about 17-19 days of pregnancy.Trypsinized embryonic cells were first grown in large vessels and then transferred into stoppered Carrel flasks 5 cm. in diameter. Continuous lines of neoplastic cells were also grown in Carrel flasks. Some information on the origin

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DDT must be evaluated as a weak carcinogen.One of the most widely used pesticides, DDT, continues to be a subject of increasing interest. The first experimental observation on the blastomogenic action of DDT in rats was made by Fitzhugh and Nelson in 1947. Since then reports on the carcinogenic effect of DDT in experiments have multiplied (Kemeny and Tarjan, 1966;Halver, 1967; Fitzhugh, 1969; Innes et al., 1969;Tarjan and Kemeny, 1969). The tumours that appeared in the treated animals were principally hepatomas, lung adenomas and lymphomas. However, in some experiments the blastomogenic effect of DDT was not substantiated (Durham, 1963 ; correspondence of Terracini and Tarjan, 1970;Agthe et al., 1970).In our laboratory it has been shown that diffuse and focal proliferation, adenomatous focal growth and, later, adenomas developed in lung organ cultures of foetal mice, rats and golden hamsters, the mothers of which had been treated with urethane, blastomogenic nitrosamines or hydrocarbons during the final period of pregnancy (Kolesnichenko, 1966(Kolesnichenko, , 1971(Kolesnichenko, , 1972 Smetanin, 1969;Shabad et al., 1971). The sameexperimental model was used to evaluate the possible carcinogenic effect of DDT.Organ cultures of foetal lung tissue from strain A mice exposed to DDT through the transplacental route showed intensive growth as compared to controls. A dose of 50 ppm of DDT induced epithelial preadenomatous lesions (diffuse hyperplasia and focal proliferation) in the first generation (F,) in 32.2 %. A progressively higher incidence of these lesions was observed at a dose level of 10ppm in F1 (8.9%), F, (16.4%) and F, (39.3 %) generations. However, the incidence dropped in the F4 (30.1%) and FS (20.1%) generations (Shabad et al., 1972). This paper deals with the results of a parallel study in vivo of the effect of DDT, especially on lung turnorigenesis in the same five generations of mice. In these multigeneration experiments we attempted to compare our results in organ culture in vitro and in mice in vivo, and evaluate the possible blastomogenic effect of the pesticide DDT.

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