Development of a model of tissue with potentially malignant disorders (PMD) in the hamster cheek pouch to explore the long-term potential therapeutic and/or toxic effects of different therapeutic modalities.
OBJECTIVE
Given that locoregional recurrences developing from a tissue with potentially malignant disorders (PMD) in oral mucosa are a frequent cause of therapeutic failure, and that tissue with PMD is dose-limiting, the aim of the present study was to develop a model of tissue with PMD to evaluate the long-term therapeutic/toxic effects of different therapeutic modalities.


METHODS
We evaluated 5 carcinogenesis protocols based on topical application of the carcinogen dimethyl-1,2-benzanthracene in the hamster cheek pouch, twice a week for 4, 6, 7, and 8 weeks and the classical 3 times a week for 12 weeks.


RESULTS
Long-term follow-up (8 months after protocol completion) was only possible with the 4- and 6-week carcinogenesis protocols. Tumour development increased progressively with time and aggressiveness of the carcinogenesis protocols. The time at which tumours developed in > or =90% of the animals was at protocol completion (T0) for the 12-week protocol, 1 month post-T0 for the 8-week protocol, 3 months post-T0 for the 7-week protocol and 4 months post-T0 for the 6-week protocol. <40% of the animals in the 4-week protocol developed tumours within the 8 months follow-up period. DNA synthesis rose as a function of time and protocol aggressiveness.


CONCLUSIONS
The 6-week carcinogenesis protocol was selected for long-term studies of different therapeutic modalities in tissue with PMD because it permitted long-term follow-up and guaranteed tumour development in > or =90% of the animals.
Heber
Elisa M
EM
Department of Radiobiology, National Atomic Energy Commission, Av. General Paz 1499, B1650KNA San Martin, Provincia de Buenos Aires, Argentina.
Monti Hughes
Andrea
A
Pozzi
Emiliano C C
EC
Itoiz
Maria E
ME
Aromando
Romina F
RF
Molinari
Ana J
AJ
Garabalino
Marcela A
MA
Nigg
David W
DW
Trivillin
Verónica A
VA
Schwint
Amanda E
AE
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D002610:Cheek / Q000473:pathology*; D006224:Cricetinae; D004195:Disease Models, Animal; D009061:Mouth Mucosa / Q000473:pathology*; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000473:pathology*
D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene