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Four 1-theta-D-arabinofuranosylcytosine (ara-C)-and one dimethylnitrosamine-transformed Syrian hamster cell lines were established. All produced tumors when inoculated into newborn hamsters. Specific chromosome changes were found in these lines consistent with changes observed recently by other investigators. Clones that had either high or low malignant potential were derived from two fibrosarcomas produced by one of the ara-C-transformed cell lines. The expression of malignancy in these clones was associated with an excess of 57 chromosomes over 73 chromosomes.

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Cultured epithelial cells from human skin generally had 3-to 30-fold more hydrocarbon-metabolizing activity than fibroblasts from skin of the same donor. This activity was constant for up to 55 days in primary culture but was lost rapidly upon physical subdivision of the cultures. Treatment of primary mixed fibroblasts and epithelial cell cultures with methylcholanthrene, but not phenanthrene, led to development of actively growing fibroblastic cultures with many heteroploid cells. Unique marker chromosomes, stable over a number of cell population doublings, were identified in several of the heteroploid cell strains. Pure cultures of fibroblasts from the same donors did not undergo heteroploid conversion in response to methylcholanthrene. Spontaneously occurring heteroploidy in logarithmic phase human fibroblasts is a rare event; thus, heteroploid conversion may be a useful marker for chemical transformation of human cells. Because methylcholanthrene seems to have little transforming effect on human skin fibroblasts, human skin epithelial cells, because of their hydrocarbon-metabolizing activity, may serve to convert methylcholanthrene from a distal to an ultimate carcinogenic form.Chemically induced transformation of human cells has been difficult to achieve (1, 2) and seldom has been reported (1, 3, 4). In the two cases in which transformation was reported, the first was in diploid human cells derived from a neurofibrosarcoma (1, 3) and the second was in an aneuploid cell line established from an osteosarcoma (4). Thus, chemically induced transformation of human cells derived from nontumor tissue has not been reported.Lack of aryl hydrocarbon hydroxylase activity has been suggested as a possible mechanism whereby human fibroblasts resist transformation by carcinogenic aromatic polycyclic hydrocarbons (5). Human embryo cultures containing a high percentage of epithelial cells have been shown to have more such activity than do fibroblast cultures from the same donors (6, 7), and it has been suggested that skin epithelial cells may be the targets of choice for chemical transformation with certain classes of carcinogens (7). Human skin epithelial cells used for this purpose were found to be sensitive to the toxic effects of polycyclic hydrocarbons, but no cell transformation was noted (5-8).In this study, we have used primary human skin mixed cell cultures consisting of individual colonies containing predominantly epithelial or fibroblastic cells. Evidence is presented for clonal evolution of aneuploid populations of fibroblast cells after methylcholanthrene (MCA) treatment and for the importance of the hydrocarbon-metabolizing activity (HMA) provided by epithelial cells.MATERIALS 2451connective tissue and then minced with scissors in a small volume of growth medium [Eagle's minimum essential medium containing 1 mM sodium pyruvate, 0.1 mM nonessential amino acids, 2 mM glutamine, 100 units of penicillin per ml, 100 ,ug of streptomycin per ml, 50 ,g of kanamycin per ml, and 10% (vol/vol) heat-inactivated f...