In this study the development of aristolochic acid (AA) induced tumors in rats with and without diallyl sulfide (DAS) was studied. Experiments were also conducted to establish the effects of DAS administration on AA-derived DNA single-stranded regions and DNA adduct formation in the forestomach of such animals. Forestomach, urinary bladder and thymus tumors were induced in male BD-6 rats after oral treatment for 12 weeks with AA (2 x 10 mg/kg/week). Administration of 150 mg/kg DAS intragastrically 4 h prior to AA treatment reduced significantly the number of rats that developed forestomach tumors (6-9 months after the start of experiment). The incidence of AA-induced forestomach tumors was 10% (two out of 20 rats) after co-administration of DAS and 60% (12 out of 20 animals) when AA was administered alone. The high dose of DAS (2 x 150 mg/kg) markedly inhibited the formation of squamous cell carcinomas in the forestomach. However, the thioether did not prevent the formation of forestomach and urinary bladder papillomatosis. Additionally, DAS co-administration decreased the accumulation of single-stranded regions in rat forestomach DNA. Using the nuclease P1 enhancement method of the 32P-postlabeling assay, a decrease in the level of AA-derived adducts was also detected after co-administration of DAS. We conclude that the decrease of DNA damage after DAS co-administration is associated with the delay in conversion of papillomas to malignant forestomach tumors.
The chromosomal proteins of rat liver were studied by SDS-gel electrophoresis during the process of nitrosomorpholine-induced hepatocarcinogenesis, in the primary hepatomas thus obtained, and in their metastases. It was found that an increased proteolytic activity was present in liver homogenates from carcinogen-fed animals which caused differences between the nonhistone chromosomal proteins of control and carcinogen-treated livers. These differences disappeared in the presence of the protease inhibitor PMSF. In the primary hepatomas slight quantative changes were observed: an increased amount of two proteins of 43000 and 63000 daltons molecular weight, respectively, and a decrease in the histone subfraction H 1 degrees. In the metastases both quantative and qualitative differences were detected: a strong decrease in the protein bands corresponding to the contractile proteins alpha-tubulin, beta-tubulin, and actin; an increased content of the 63000 dalton protein; the appearance of new proteins of approximately 60000, 90000, and 120000 daltons molecular weight, and the complete disappearance of histone H 1 degrees.
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