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Tumor rejection in experimental animals treated with radioprotective thiols
Abstract:
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 tow 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 thioyls, S-2-(3-aminopropylamino)ethylphosphorothioic acid or S-(2-ethylguanidine)phosphorothioci 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.
Insights
Mercaptoalkylamine thiols effectively inhibited or caused necrosis ("oncodieresis") in experimental solid tumors. Optimal results required early treatment and specific compound structures, with some combinations proving less effective.
Area of Science:
- Biomedical research
- Experimental oncology
- Pharmacology
Background:
- Systemic treatment with mercaptoalkylamine thiols has shown significant effects on various solid tumors in experimental models.
- These compounds are known to bind cellular sites via a two-point attachment involving thiol and amino groups.
Purpose of the Study:
- To investigate the efficacy of mercaptoalkylamine thiols in treating experimental solid tumors.
- To explore the structure-activity relationship of these compounds and their impact on tumor response.
- To evaluate the influence of treatment timing, animal sex, and combination therapies on tumor rejection.
Main Methods:
- Systemic administration of various mercaptoalkylamine thiols and their derivatives to experimental animals bearing solid tumors.
- Investigation of tumor growth inhibition and "oncodieresis" (necrosis and sloughing).
- Assessment of factors including treatment initiation time, animal sex, and co-administration with other agents like radioprotectants and serotonin.
Main Results:
- Mercaptoalkylamine thiols demonstrated efficacy against five investigated solid tumors, inducing either growth inhibition or oncodieresis.
- The activity of cysteamine was dependent on its native form; alkylated derivatives or cystamine (disulfide dimer) were inactive.
- Early treatment (day of inoculation) and male mice showed better tumor rejection. Combination with certain radioprotectants reduced efficacy, while phosphorylated thiols showed synergy with serotonin.
Conclusions:
- Mercaptoalkylamine thiols represent a promising class of compounds for experimental solid tumor treatment, with specific structural requirements for activity.
- Treatment timing and host factors significantly influence therapeutic outcomes.
- Further research into the mechanism of action and optimization of combination therapies, particularly with phosphorylated thiols and serotonin, is warranted.
