Polycyclic aromatic hydrocarbons, such as Benzo(a)pyrene (BaP), are known mammary carcinogens in animal models and may be involved in the etiology of human breast cancer. BaP is primarily generated from the combustion of fossil fuels from vehicle exhausts, industrial power generation and incinerators. Upon inhalation, BaP is metabolized to reactive intermediates including reactive oxygen species which lead to DNA strand breaks. These genetic perturbations are associated with cancer formation. Diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) are naturally occurring organosulfur compounds found in garlic which has been shown to prevent cancer in several animal models via metabolic modulation. Previously, we have shown that DAS, DADS, and DATS inhibited BaP induced DNA strand breaks and lipid peroxidation. We hypothesized the increased expression of superoxide dismutase (SOD) and glutathione (s) transferase (GST) plays a role in the inhibition of BaP induced lipid peroxidation and DNA strand breaks. To test this hypothesis, breast epithelial cells (MCF-10A) were treated with BaP (5µM), DAS(10µM) and DAS(10µM) for 3 hours followed by a 24 hour treatment with BaP (5µM). Cells were also treated with DMSO as a vehicle control. A SOD kit from Sigma and a GST kit from Cayman were used to determine enzyme activity. BaP, DAS and BaP/DAS induced the activity of SOD by 7.0, 1.5 and 2.0 fold respectively. BaP, DAS and BaP/DAS induced the activity of GST by 2.2, 1.8 and 2.0 fold respectively. This induction in activity of detoxification enzymes may play a role in inhibiting BaP induced toxicity and/or carcinogenicity.
This research was supported by NIH/RCMI Grant # G12 RR03020.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA