phorbol-12-13-didecanoate and Carcinoma--Squamous-Cell

A model of oral mucosal carcinogenesis using the water-soluble carcinogen 4-nitroquinoline-1-oxide (4NQO) was combined with a model of oral mucosal candidosis to examine the ability of Candida albicans to promote the development of neoplasia in suitably initiated epithelium. Sprague-Dawley rats were initiated by the application of 4NQO to their palatal and tongue mucosa 3 times weekly for 4 weeks. The animals then received either application of a phorbol ester to act as a promoter, induction of experimental oral mucosal infection with C. albicans, or no further procedures. Animals were killed at 34 or 52 weeks and the tongues and palates sectioned for light-microscopic examination. Control groups with no treatment, mucosal infection only, phorbol ester application only, 4NQO with the tetracycline or vehicle application only were also used. The development of carcinoma in the experimental groups was similar to that in the positive control groups, indicating that the particular strain of Candida used had a similar ability to promote neoplastic changes as the known promoter phorbol-12,13-didecanoate and caused neoplastic changes to occur by week 34 with no additional lesions occurring by week 52. This indicated that the speculation that strains of C. albicans may participate in causing neoplastic transformation in humans was well founded.

Topics: 4-Nitroquinoline-1-oxide; Animals; Candida albicans; Carcinogens; Carcinoma, Squamous Cell; Male; Palatal Neoplasms; Phorbol Esters; Rats; Rats, Inbred Strains; Tongue Neoplasms

While there is considerable evidence that skin carcinogenesis proceeds as a step-wise series of changes, little evidence is available to indicate that a similar mechanism applies to oral mucosal carcinogenesis. In the current study, a mouse model of mucosal carcinogenesis was used to examine the effects of repeated applications of the phorbol ester phorbol-12,13-didecanoate (PDD) following various periods of treatment with the carcinogen 4-nitroquinoline-1-oxide (4NQO). All animals were histologically examined at 50 weeks. Oral epithelial dysplasia was seen in animals treated with 4NQO for as little as 2 weeks, and oral squamous cell carcinomas developed in all animals treated with 4NQO for 16 weeks. In those mice treated with PDD as well, carcinomas developed in mice receiving as little as 2 weeks treatment with 4NQO, and 100% of mice treated with 4NQO for 12 weeks, followed by PDD treatment, developed carcinomas. The results indicate that irreversible changes in the oral mucosa of mice occur relatively early during treatment with 4NQO, and the development of carcinomas can be enhanced with subsequent PDD treatment, giving an indication of staged carcinogenesis in this model system.

Topics: 4-Nitroquinoline-1-oxide; Animals; Carcinoma, Squamous Cell; Epithelium; Male; Mice; Mice, Inbred CBA; Mouth Mucosa; Mouth Neoplasms; Nitroquinolines; Phorbol Esters; Time Factors