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© 1995 Oxford University Press

research-article

Studies on the Tumor Initiation/Promotion Potential of Six Middle Distillates (MDs) in Mouse Skin

H. JUNGEN*,1, W. MELLERT{dagger} and R. WENZEL-HARTUNG{ddagger}

*DGMK German Society for Petroleum Sciences and Coal Chemistry D-20095 Hamburg, Germany {dagger}Department of Toxicology, BASF Aktiengesellschaft D-67056 Ludwigshafen, Germany {ddagger}H. O. Schümann GmbH and Co. KG D-20457 Hamburg, Germany

Received March 25, 1994; accepted December 15, 1994

Six middle distillates (MDs) were tested for tumor initiating/promoting activity after application to the skin of 30 male CD-1 (ICR) BR mice per group. As the control, 7,12-dimethylbenz[a]-anthracene (DMBA) was used for initiation followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) for promotion. For assessing the tumor-initiating activity, 50 µl of neat MDs was administered for 5 days with subsequent TPA promotion. In the promotion bioassay, after DMBA initiation 50 µl of the neat MDs was administered twice weekly until Week 28. For the examination of complete carcinogenic activity, one MD was given without DMBA initiation. Hyperkeratosis, hyperplasia, and dermal inflammation, occurring during the initiation with the MDs, were completely reversible during the 2-week treatment-free period after initiation. Similar skin findings were observed during promotion with the MDs. Regarding the number of affected animals and the severity of the response, TPA was more irritating than the MDs. The initiation study revealed skin tumors for the DMBA/TPA control (30/30), MID 57,389 (14/30), MD 57,396 (5/30), MD 57,383 (4/30) and MD 57,324 (2/30). The promotion study revealed tumor induction by MDs 57,389 (9/30), 57,324 (1/30), 57,393 (1/30), and 57,396 (1/30). Two of 30 animals treated with MD 57,389 developed tumors without DMBA initiation thus indicating that it also is a complete carcinogen. M 57,399 caused neither initiating nor promoting effects. The tumors observed were diagnosed histopathologically predominantly as squamous cell papillomas. Furthermore, the results confirmed the assumption that (i) a high mutagenicity index (MDs 57,389, 57,396, 57,383) correlates with tumor-initiating activity and (ii) a relatively high dodecane content (MDs 57,389, 57,324, 57,393, 57,396) correlates with tumor-promoting activity.


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