Hamster cheek pouch as a bioassay system in short term screening for tumor initiating and promoting agents. Optimization of parameters and observations of effects of cytotoxicity on tumor promotion by retinyl acetate.
The effects of various conditions on tumor initiation by 7,12-dimethylbenz(a) anthracene (DMBA) and promotion by retinyl acetate (RA), both in dimethylsulfoxide, were studied by topical application in hamster cheek pouch. The variables studied were: initiation and promotion time and schedule (alternate vs consecutive day paintings), concentration of DMBA used for initiation, and cytotoxicity. Spontaneous tumor progression followed by regression was observed in control animals which had been initiated for 4 weeks with 0.2% DMBA, but not given subsequent promotion treatment. Spontaneous progression was not observed in control animals which had been given only 2 weeks of initiation treatment, although RA both promoted new tumors and caused progression of benign hyperplastic lesions (BHLs) to advanced tumors. The approximate optimal conditions for obtaining acceptable tumor yields from promotion while minimizing associated errors and time periods were: 2 weeks of initiation with 0.2% DMBA and 4 weeks of promotion with 0.05 M RA, both with alternate day painting schedules. Reducing the initiation period but painting on consecutive days caused intolerable cytotoxicity and lowered tumor yields although the total dose of DMBA was kept constant. Increasing initiation time increased tumor yield in unpromoted controls as well as promoted groups, thus increasing errors in net yield from promotion. Similar results were obtained from doubling concentration of DMBA and halving initiation time. Reducing promotion time to below 4 weeks lowered tumor yield due to insufficient time for tumor development. Increasing promotion time to 6 weeks lowered tumor yield in both control and promoted groups, possibly due to spontaneous regression. Cytotoxicity enhanced progression to advanced tumors all of which were inflamed polypoid fibrovascular lesions. The cytotoxicity of DMBA was far greater than that of RA. Evidence is presented that tumor promotion by RA is not due to cytotoxicity. The hamster pouch system may afford an excellent short term mammalian screening test for tumor initiating and promotion agents.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens; D002610:Cheek; D055598:Chemical Phenomena; D002621:Chemistry; D006224:Cricetinae; D004224:Diterpenes; D005260:Female; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D000084562:Retinyl Esters; D013997:Time Factors; D014116:Toxicology / Q000379:methods*; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000633:toxicity
D002273:Carcinogens; D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C009166:retinol acetate; D015127:9,10-Dimethyl-1,2-benzanthracene