Alterations in Benzo(a)pyrene induced DNA damage via Organosulfide Compounds in MCF-10A cells
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abstract
The Organosulfide compounds (OSCs) of garlic, Diallyl sulfide (DAS), Diallyl disulfide (DADS) and Diallyl trisulfide (DATS) have chemopreventive effects on several cancers including breast cancer. Previously we have shown that coexposure of benzo(a)pyrene(BaP), and OSCs has lead to a decrease in lipid peroxides thereby reducing DNA strand breaks while inducing cell cycle arrest in MCF10A cells. Therefore, these data led us to hypothesize that the mechanism of OSCs attenuation of BaP induced DNA damage in these cells occurs via alterations in the expression of cell cycle and DNA repair genes. To prove this hypothesis, CDKN1A (p21), BCL2L1, DNA polymerase beta and epsilon expression were determined via RTPCR and protein expression via western blot analysis in MCF10A cells after 24 hours using the following treatments: 0.1% DMSO control, 1 M BaP alone, 60 M OSC, or 1 M BaP/60 M OSC coexposure. After coexposure to DATS, a significant (p<0.05) increase was observed in p21, BCL2L, DNA polymerase beta, and epsilon gene expression when compared to control and BaP alone. DADS coexposure caused a significant (p<0.05) increase in DNA polymerase beta and p21 gene expression when compared to control and BaP alone. Protein expression studies indicated that coexposure to DAS, DADS and DATS significantly (p<0.05) increased DNA polymerase beta expression when compared to control and BaP alone. These results indicate that the chemopreventive effects observed in OSCs may be occurring via an increase in gene and protein expression of DNA repair genes involved in base excision repair.
