Antitumor studies of 2-amino-2-thiazoline and other tumor-modifying agents.

2--amino-2-thiazoline (AT) and 1-thiazolidine-4-carboxylate (TC, thioproline), which have been previously proposed as agents of reverse transformation, have been examined as antitumor agents in several rodent tumor systems. AT administration reduced tumor incidence in sym-dimethylhydrazine treated outbred ICR Swiss female mice and doubled the survival of DBA/2Ha female mice infected with polycythemic Friend leukemia virus. Indomethacin, pentoxyphylline, RA233 and diethyldithiocarbamate (DTC), with potential for altering host or tumor prostaglandin levels, platelet aggregation and host immunity, respectively, ranged from marginally effective to ineffective against Friend virus infection. AT was, however, ineffective against 4 other induced and transplanted mouse tumors and did not notably increase differentiation or decrease transformation in any of several tumor cell systems. No in vitro or in vivo tumor system was found to be more than marginally affected by TC. Thus, AT alone was of significant antitumor activity in inhibiting late stages of viral- or carcinogen induced tumor progression, but could not be demonstrated as an agent of reverse transformation.

Further fractionation and co-promoting activity of the large molecular weight components of aqueous tobacco extracts.

Earlier studies showed that aqueous extracts of tobacco exhibit tumor promoting activity. The activity required the simultaneous presence of two agents, one of which was methanol soluble and the other, methanol insoluble. In this study, the 80% methanol insoluble fraction was further fractionated using dialysis through controlled pore membranes. Each resulting sub-fraction was then combined with the methanol soluble fraction and tested as a promoting stimulus in mice treated with 7,12-dimethylbenz[a]anthracene. The subfraction (D) with a presumptive molecular weight greater than 13,000 produced a significantly higher tumor incidence and tumor yield together with a significantly shorter latent period than the other subfractions. D contained about 12% of the total 80% methanol insoluble material. All of the other subfractions exhibited significant but less pronounced co-promoting activity.

Tumor-promoting activity of certain extracts of tobacco.

Tumor-promoting activities of extracts of fluecured and cigarette tobacco were evaluated. Initially, fluecured tobacco was extracted consecutively with hexane, chloroform, acetone, ethyl alcohol, methyl alcohol, and water; and the extracts were tested for tumor-promoting activity on mouse skin. The hexane and chloroform extracts were fractionated on silicic acid, and the fractions were devoid of tumorigenic activity. The acetone and alcohol extracts showed marginal activity. Subsequently, chloroform-extracted cigarette tobacco was extracted with water, and the aqueous extract was partitioned by solvent precipitation methods. Bioassay results showed tumor-promoting activity for the aqueous extract, with tumors in 38% of the animals. The aqueous extract appeared about five times as active as smoke condensate derived from an equal weight of tobacco.

Cocarcinogenic activity of peroxy compounds.

Peracetic acid was a potent tumor promoter and a weak complete carcinogen on the skin of female ICR Swiss mice. "Decomposed peracetic acid" was inactive as a tumor promoter, as were 3% [hydrogen peroxide and 5%] urea peroxide; 1% perbenzoic acid and m-chloroperbenzoic acid were active tumor prototers.