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Most anticancer drugs are mutagenic/carcinogenic. A possible exception is diallyl trisulfide (DAT), a component of garlic, which inhibits growth of transplantable tumors in vitro and in vivo and mutagenicity and carcinogenicity of genotoxic agents. It is an antimutagenic anticancer chemical. Its modulating effect on induction of UDS by mutagenic mitomycin C (MMC), cyclophosphamide (CP), and cis-diamine dichloroplatin (DDP) was investigated with the assay in primary cultures of Wistar rat hepatocytes by autoradiographic technique. Results showed that MMC (1-10 mumol/L), CP (0.316-3.16mmol/L), and DDP(3.16-31.6mumol/L) resulted in a significant induction of dose-dependent UDS and that DAT (0.5-4.0 mumol/L) significantly enhanced induction of UDS by MMC, CP and DDP while DAT itself did not. A dose-response relation was also observed between the dosage of DAT and the enhancement of induction of UDS. Hepatocellular enzymes for metabolic activation of indirect mutagens may not be involved in the enhancement of UDS-induction since DAT also increased UDS level induced by direct mutagen DDP. DAT promotes UDS induction probably by increasing repair of damaged 4-DNA. DAT, an anti-infection antibiotic, may be used in cancer chemotherapy to alleviate the adverse side effects of chemotherapeutic agents with mutagenic/carcinogenic activities.

Gastric cancer is the leading cause of death from cancer in China. Samples of fish sauce, a traditional seasoning, were collected in the high-risk area for gastric cancer in the Fuzhou area, Fujian Province. When fish sauce samples were nitrosated at pH 2.0, direct mutagenicity and high contents of N-nitrosamide were detected (30.9-78.0 microM); the N-nitrosamide content of three samples of fish sauce made in Guangdong and purchased from a market outside Fujian were low (2.1-6.0 microns). When the nitrosated fish sauce extract was given to newborn rats by gavage, dysplasia and adenocarcinoma were induced in the glandular stomach in the 4th and 16th experimental week, respectively. N-Nitrosamides were also found in fasting gastric juice from patients with chronic gastritis in the high-risk area of Putian. The mean concentration of total N-nitrosamides in the extracts correlated with the severity of gastritis in the stomach. These findings indicate that N-nitrosamides may play an important role in causing gastric cancer in China.

In order to elucidate the mechanism of tumor prevention of beta-carotene, its effect on sister chromatid exchanges (SCE) induced by MNNG in cultured V79 cells, under condition free of the enzyme system to convert beta-carotene into vitamin A, was studied. It was found that SCE level was significantly increased by high doses beta-carotene (10(-5)-10(-4) M) and the enhancement of SCE was restored to its original level by addition of alpha-tocopherol (final concentration 2 micrograms/ml). This may be due to the latter inhibiting the oxidation of beta-carotene and reducing the amount of oxidated carotene, which is toxic for cultured cells. Combination of beta-carotene and alpha-tocopherol at low doses inhibited SCE induced by MNNG (P less than 0.05) but no protective activity was observed when used separately. It was also found that beta-carotene (2 x 10(-7) M) and retinol (16 micrograms/ml) inhibited SCE induced by aflatoxin B1, which is activated by S-9 mixture. The present data clearly show that the antitumor activity of beta-carotene may be attributed to both itself and its degraded compound vitamin A, and may take part in the initiation of carcinogenesis. Combination of beta-carotene and other cancer preventive drugs is more effective and safer than it used individually.