Nuclear enlargement produced in mouse skin by carcinogenic mineral oils

Ten oils of differing origin, degree of refinement and carcinogenicity, were examined for their ability to produce nuclear enlargement in mouse skin following repeated topical exposure over a 3 day period. Application of the oils was made in a vehicle of methyl ethyl ketone incorporating a promoter and assessment of epidermal nuclear size was made on tissue sections using a Quantimet 720 image analyser. One of the oils reported to be non-carcinogenic, was examined initially and its inability to induce enlargement of nuclei beyond the size seen in hyperplastic skin was confirmed. The same oil was then examined in combination with benzo(a)pyrene (BaP) and, from the dose-response obtained, it was clear that the oil did not prevent BaP induced nuclear enlargement. The other nine oils were examined by comparing them with the previously tested non-carcinogenic oil. Two oils gave rise to clear nuclear enlargement; these were non-solvent refined and gave rise to skin tumours in reported long-term studies. One solvent-refined oil, which gave a single papilloma in reported long-term studies, gave borderline (non-significant) nuclear enlargement; whereas the other solvent-refined oils, including five reported as non-carcinogenic and one reported as having weak (questionable) carcinogenic activity, gave no nuclear enlargement. Further examination of the data suggested that, within the limited series of oils examined, nuclear enlargement under these test conditions correlated well with carcinogenicity and might be used for predicting the skin carcinogenicity of an oil. Studies on a further 23 oils, on which long-term studies have been carried out but not published, support this conclusion.