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Enhancement by Organosulfur Compounds from Garlic and Onions of Diethylnitrosamine-induced Glutathione S-Transferase Positive Foci in the Rat Liver¹

First Department of Pathology [N. T., T. M., T. O., S. F.] and Second Department of Biochemistry [Y. Y., S. O.], Osaka City University Medical School, Asahi-machi, Abeno-ku, Osaka 545, Japan; Department of Community Health Science, Saga Medical School, Saga 849, Japan [T. H.]; and Department of Oncological Pathology, Cancer Center, Nara Medical University, Nara 634, Japan [D. N., Y. K.]

Ten organosulfur compounds from garlic and onions were studied for their modifying effects on diethylnitrosamine-induced neoplasia of liver in male F344 rats using the medium-term bioassay system of Ito based on the two-step model of hepatocarcinogenesis. Carcinogenic potential was scored by comparing the number and area per cm² of induced glutathione S-transferase placental form-positive foci in the liver with those of the corresponding control group given diethylnitrosamine alone. In experiments 1 and 2, high doses of diallyl sulfide, diallyl trisulfide, allyl methyl sulfide, allyl methyl trisulfide, and dipropyl sulfide had enhancing effects on focus formation. In contrast, high doses of methyl propyl disulfide and propylene sulfide significantly decreased the number of glutathione S-transferase placental form-positive foci. In the third experiment, combined treatment with the five chemicals that had enhancing activity were fed at low doses and increased the induction of glutathione S-transferase placental form-positive foci. To investigate the mechanism of the modifying effect on hepatocarcinogenesis, ornithine decarboxylase activity was measured in diallyl sulfide-, allyl methyl sulfide-, and dipropyl sulfide-treated liver tissue without prior initiation with diethylnitrosamine, and its activity was increased compared to controls. Spermidine/spermine N¹-acetyltransferase activity was not significantly changed. Formation of 8-hydroxydeoxyguanosine, a DNA adduct generated by activated oxygen species, and lipid peroxidation (2-thiobarbituric acid-reacting substance production) were also not changed. These results suggest that the promoting effect could be caused by increased cell proliferation with increased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is appropriate to consider not only the possible protective role of garlic and onions but also their enhancing effects.

¹ This study was supported by Grant-in-Aid of Cancer Research from the Ministry of Health and Welfare.

² To whom requests for reprints should be addressed.

Received 8/18/93. Accepted 4/ 5/94.

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