Diallyl trisulfide (DATS) is a garlic organosulfide that is toxic to cancer cells, however, little is known about its effect in the initiation phase of carcinogenesis. We sought to determine whether DATS could inhibit the carcinogen, benzo(a)pyrene (BaP), from inducing precancerous activity, in vitro. MCF-10A cells were either pre-treated (PreTx) or concurrently treated (CoTx) with 1 μM BaP, and 6 or 60 μM DATS for up to 24 hours. The DATS 6 and 60 μM CoTx inhibited BaP-induced cell proliferation by an average of 71.1 and 120.8%, respectively, at 6 hours. The 60 μM DATS pretreatment decreased BaP-induced G2/M cell cycle transition by 127 %, and reduced the increase in cells in the S-phase by 42%; whereas 60 μM DATS CoTx induced a 177% increase in cells in G1. DATS effectively inhibited (P<0.001) BaP-induced peroxide formation by at least 54%, which may have prevented the formation of BaP-induced DNA strand breaks. In this study, we reveal mechanisms involved in DATS inhibition of BaP-induced carcinogenesis, including inhibition of cell proliferation, regulation of cell cycle, attenuation of ROS formation, and inhibition of DNA damage. At the doses evaluated, DATS appears to be an effective attenuator of BaP-induced breast carcinogenesis, in vitro.

Polycyclic aromatic hydrocarbons (PAHs) and their oxygenated derivatives are ubiquitously present in diesel exhaust, atmospheric particulate matter and soils sampled in urban areas. Therefore, inhalation or non-dietary ingestion of both PAHs and oxy-PAHs are major routes of exposure for people; especially young children living in these localities. While there has been extensive research on the parent PAHs, limited studies exist on the biological effects of oxy-PAHs which have been shown to be more soluble and more mobile in the environment. Additionally, investigations comparing the metabolic responses resulting from parent PAHs and oxy-PAHs exposures have not been reported. To address these current gaps, an untargeted metabolomics approach was conducted to examine the in vivo metabolomic profiles of developing zebrafish (Danio rerio) exposed to 4 µM of benz[a]anthracene (BAA) or benz[a]anthracene-7, 12-dione (BAQ). By integrating multivariate, univariate and pathway analyses, a total of 62 metabolites were significantly altered after 5 days of exposure. The marked perturbations revealed that both BAA and BAQ affect protein biosynthesis, mitochondrial function, neural development, vascular development and cardiac function. Our previous transcriptomic and genomic data were incorporated in this metabolomics study to provide a more comprehensive view of the relationship between PAH and oxy-PAH exposures on vertebrate development.

These findings point to potential targets and pathways that may be central to asthma pathogenesis and can serve as novel therapeutic targets.

Diallyl disulfide (DADS), a garlic organosulfur compound (OSC), has been researched as a cancer prevention agent; however, the role of DADS in the suppression of cancer initiation in non-neoplastic cells has not been elucidated. To evaluate DADS inhibition of early carcinogenic events, MCF-10A cells were pretreated (PreTx) with DADS followed by the ubiquitous carcinogen benzo(a)pyrene (BaP), or co-treated (CoTx) with DADS and BaP for up to 24 hours. The cells were evaluated for changes in cell viability/proliferation, cell cycle, induction of peroxide formation, and DNA damage. BaP induced a statistically significant increase in cell proliferation at 6 hours, which was attenuated with DADS CoTx. PreTx with 6 and 60 μM of DADS inhibited BaP-induced G2/M arrest by 68 and 78%, respectively. DADS, regardless of concentration or method, inhibited BaP-induced extracellular aqueous peroxide formation within 24 hours. DADS attenuated BaP-induced DNA single strand breaks at all time points through both DADS Pre- and CoTx, with significant inhibition for all treatments sustained after 6 hours. DADS was effective in inhibiting BaP-induced cell proliferation, cell cycle transitions, ROS, and DNA damage in a normal cell line, and thus may inhibit environmentally induced breast cancer initiation.