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Antineoplastic Effect of Chlorpromazine in Chemical Carcinogenesis in the Hamster Cheek Pouch

Departments of Hematology [A. P.] and Pathology [I. S. L.], Hadassah University Hospital and Hebrew University Medical School, Jerusalem, Israel

Hamster cheek pouches were treated topically with 9,10-dimethyl-1,2-benzanthracene (DMBA) alone, in combination with chlorpromazine (CPZ), or following pretreatment with CPZ.

After 9 weeks of application of 1.2% CPZ and 0.5% DMBA simultaneously, only one microscopic focus of intraepithelial carcinoma was present in one of the six animals, whereas in the six animals treated with DMBA alone, nine atypical papillomas and three invasive carcinomas were present. After 12 weeks, only one carcinoma and one atypical papilloma were found in two of the six animals treated with CPZ and DMBA, in contrast to the finding of 18 carcinomas and 8 atypical papillomas in the pouches after DMBA alone. The dose-related effect of CPZ was demonstrated when, in a similar procedure, with 0.6% CPZ, only partial inhibition of carcinoma formation was obtained after 9 and 12 weeks.

When the pouches were pretreated with topical 1.2% CPZ for 12 weeks prior to DMBA application, almost complete inhibition of tumor formation was obtained.

The antineoplastic action of CPZ is reviewed and the membrane and lysosomal stabilizing properties and dose relation of this drug are discussed. It is suggested that the inhibitory effect of CPZ may be related to decreased permeability of cellular and subcellular membranes, resulting in decreased permeation of the carcinogen into the cellular structures. It is also possible that stabilization of lysosomes is achieved, with decreased release of lysosomal enzymes known to influence nuclear activity and with consequent delay in cell division.

¹ Supported by a grant from the Research Promotion Fund of the Histadrut (General Federation of Jewish Labour).

² Supported by a grant from Mr. Michael Kerber, Toronto, Canada.

Received 3/ 3/72. Accepted 6/ 1/72.

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