Abstract 4245: Effects of black raspberries extract on DNA repair capacity and metabolic activation/detoxification of the tobacco carcinogen dibenzo[def,p] in human oral cells

Abstract

We previously reported that black raspberries (BRB) powder inhibits dibenzo[def,p]chrysene (also known as dibenzo[a,l]pyrene; DBP)-induced DNA damage, mutagenesis and carcinogenesis in the mouse oral cavity. The effects of BRB on the capacity of DNA repair was investigated in an established in vitro system using HeLa cells to assess the DNA repair capacity. We found that pre-treatment of Hela cells with BRB extracts (BRBE) can enhance the nucleotide excision repair (NER) of a bulky DNA adduct derived from the tobacco oral carcinogen benzo[a]pyrene by ~24% and this effect is correlated with the enhanced expressions of NER factors XPA and XPB. The NER activity of guanidinohydantoin (Gh), an oxidatively-derived non-bulky DNA lesion, is also enhanced by ~24%, while its base excision repair activity is enhanced by only ~6%. Using human oral leukoplakia (MSK-Leuk1) and oral squamous cell carcinoma SCC1483, we demonstrated that BRBE can inhibit DNA damage induced by DBP through the induction of GSH synthesis and enhancing GSH conjugates thereby inhibiting DNA damage. The effects of BRBE in MSK-Leuk1 and SCC1483 cells were further investigated on the DNA excision repair protein ERCC1 at 1, 6 and 24 h. ERCC1 forms the ERCC1-XPF enzyme complex that participates in several DNA repair pathways. Western blot analyses revealed that BRBE induced higher ERCC1 expression in SCC1483 than those observed in MSK-Leuk1 cells in a time-dependent manner. The results of our study demonstrate that BRBE is capable of inhibiting the metabolic activation, enhancing the detoxification pathway and DNA repair capacity which are consistent with its chemopreventive activity in vivo. Supported by NIH grant #CA173465. Citation Format: Yuan-Wan Sun, Kun-Ming Chen, Ana H. Sales, Nicholas Geacintov, Karam El-Bayoumy. Effects of black raspberries extract on DNA repair capacity and metabolic activation/detoxification of the tobacco carcinogen dibenzo[def,p] in human oral cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4245.