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Tumor Rejection in Experimental Animals Treated with Radioprotective Thiols¹

Ira T. Nathanson Research Laboratories, Massachusetts Department of Public Health, Pondville Hospital, Walpole, Massachusetts 02081 [C. A. A.]; Food Chemistry Division, United States Army Laboratories, Natick, Massachusetts 01765 [J. E. W.]; and Veterans Administration Hospital and Brown University Medical School, Providence, Rhode Island 02908 [S. I.]

In experimental animals, a systemic treatment with thiols of the mercaptoalkylamine type has affected all of five solid tumors so far investigated. (Three of the tumors were transplanted into the strain of origin.) There was either inhibition of growth or "oncodieresis," i.e., a necrosis and sloughing of tumors conducive to full recovery and repair. Mercaptoalkylamines and derivatives of the type used in our experiments are known to bind to cellular sites by a two-point attachment involving both thiol and amino groups. One of these compounds, cysteamine, was active in its native, unsubstituted form, but did not bring about oncodieresis when either the amino or thiol group, or both, were alkylated. Mercaptopropylamine, the 3-carbon homolog of cysteamine, was less active. Cystamine, a disulfide dimer of cysteamine that has no free reactive sulfhydryl, did not induce any reaction. Thioglycerol, lacking a terminal amino group, had only negligible activity. Rejection was much more striking when treatment was started on the day of inoculation than when started 7 days later. Male mice rejected better than females. Results were inferior when two of the agents were given simultaneously or together with other radioprotectants, such as L-cysteine, glutathione, dimethyl sulfoxide, or reserpine. Tumor rejection was enhanced when the phosphorylated thiols, S-2-(3-aminopropylamino)ethylphosphorothioic acid or S-(2-ethylguanidine)phosphorothioic acid, were given simultaneously with the radioprotective serotonin, but there was no synergy of serotonin with the nonphosphorylated compounds S-2-aminoethylisothiouronium bromide or cysteamine. Serotonin alone did not affect the tumors.

¹ Supported in part by American Cancer Society (Massachusetts Division) Grant 1408-C, and by the Pondville Hospital Trust Fund for Cancer.

Received 4/26/74. Accepted 11/ 5/74.