Lack of initiation and promotion potential of deoxynivalenol for skin tumorigenesis in Sencar mice.
The mycotoxin deoxynivalenol (DON; vomitoxin) was tested for its potential to initiate or promote skin tumours through a two-stage treatment regimen in female Sencar mice. DON's capability for initiation was tested by applying a single topical dose (200 micrograms) followed by multiple treatments of the promoter phorbol 12-myristate 13-acetate (PMA). The test for promotion involved initiation with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) followed by multiple DON treatments (50 micrograms). Appropriate control groups were included in the study design. Mice were observed for 26 wk and skin tumours were counted. Results of the study showed that DON was not an initiator or a promoter. When DON was tested as an initiator, there were no statistically significant differences in the number of cumulative tumours or the number of tumour-bearing mice between the DON-initiated/PMA-promoted group and its control, the vehicle-initiated/PMA-promoted group. When DON was administered as a promoter, no tumours were observed. Histopathology of the skin revealed that DON induced a mild diffuse squamous hyperplasia, but there was no progression of the lesion to neoplasia.
Lambert
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LA
Division of Science and Applied Technology, US Food and Drug Administration, Washington, DC 20204.
Hines
F A
FA
Eppley
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RM
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000633:toxicity*; D000287:Administration, Topical; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000473:pathology; D003627:Data Interpretation, Statistical; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010212:Papilloma / Q000139:chemically induced* / Q000473:pathology; D011897:Random Allocation; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced*; D013154:Spleen / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000633:toxicity*; D014255:Trichothecenes / Q000008:administration & dosage / Q000633:toxicity*
D014255:Trichothecenes; D015127:9,10-Dimethyl-1,2-benzanthracene; C007262:deoxynivalenol; D013755:Tetradecanoylphorbol Acetate