Clonal origin of chemically induced papillomas: Separate analysis of epidermal and dermal components

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Abstract
A fundamental prediction of the hypothesis that critical events in tumour formation are rare is that the tumours develop by clonal expansion. This prediction has been tested by establishing the isozyme content of tumours induced in mosaic animals whose normal tissues contain two distinguishable isozyme activities. The observation that tumours contain activity associated with one or other of the two cell types present in non-neoplastic tissue has been taken to support the contention that the tumours are clonal in origin. Conversely, the presence of both isozyme activities has been taken to mean that the tumours are derived from a large number of cells. There are conflicting reports concerning the clonal origins of chemically induced epidermal tumours. In this report we present evidence that permits a critical resolution of this controversy. The neoplastic epidermal component of the tumours in mosaic animals was separated from the non-neoplastic dermal components. The neoplastic components were derived exclusively from one or other of the cell lineages present within the mosaic, while the dermal non-neoplastic tissue was shown to be derived from both cell lineages. The data support the view that, irrespective of dose or type of carcinogen, the neoplastic portion of a tumour is clonally derived and that analysis of unseparated tumours is confounded by non-neoplastic dermal tissue. The patch size (number of cells in aggregates of like cell type) was established in the target tissue, isolated epidermis. It has been previously held that the epidermal patch of chimeras is larger than that in X-chromosome-linked mosaics. We have established that this is not the case in isolated epidermis of the mouse.