The Role of Chemical Carcinogens and Their Biotransformation in Colorectal Cancer

Marchand, Loı̈c Le

doi:10.1007/978-0-387-09568-4_18

Cited by 2 publications

(2 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Biotransformation plays a pivotal role in the conversion of chemical carcinogens into reactive species that damage cellular macromolecules, interfere with signaling pathways and cause cancer [29–31]. Hence, it is conceivable that colorectal cancers are promoted by the increased intake of PAHs through dietary fat that in turn influences the biotransformation and metabolic processing of toxic chemicals.…”

Section: Introductionmentioning

confidence: 99%

Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer

Diggs

Myers

Banks

et al. 2013

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

In the US alone, around 60,000 lives/year are lost due to colon cancer. Diet and environment have been implicated in the development of sporadic colon tumors. The objective of this study was to determine how dietary fat potentiates the development of colon tumors through altered B(a)P biotransformation, using the Adenomatous polyposis coli with Multiple intestinal neoplasia mouse model. Benzo(a)pyrene was administered to mice through tricaprylin, and unsaturated (USF; peanut oil) and saturated (SF; coconut oil) fats at doses of 50 and 100 μg/kg via oral gavage over a 60-day period. Blood, colon, and liver were collected at the end of exposure period. The expression of B(a)P biotransformation enzymes [cytochrome P450 (CYP)1A1, CYP1B1 and glutathione-S-transferase] in liver and colon were assayed at the level of protein, mRNA and activities. Plasma and tissue samples were analyzed by reverse phase high-performance liquid chromatography for B(a)P metabolites. Additionally, DNA isolated from colon and liver tissues was analyzed for B(a)P-induced DNA adducts by the 32P-postlabeling method using a thin-layer chromatography system. Benzo(a)pyrene exposure through dietary fat altered its metabolic fate in a dose-dependent manner, with 100 μg/kg dose group registering an elevated expression of B(a)P biotransformation enzymes, and greater concentration of B(a)P metabolites, compared to the 50 μg/kg dose group (P<.05). This effect was more pronounced for SF group compared to USF group (P<.05). These findings establish that SF causes sustained induction of B(a)P biotransformation enzymes and extensive metabolism of this toxicant. As a consequence, B(a)P metabolites were generated to a greater extent in colon and liver, whose concentrations also registered a dose-dependent increase. These metabolites were found to bind with DNA and form B(a)P-DNA adducts, which may have contributed to colon tumors in a subchronic exposure regimen.

show abstract

Section: Introductionmentioning

confidence: 99%

Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer

Diggs

Myers

Banks

et al. 2013

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

show abstract

“…Most of these pathways are highly associated with colorectal cancer according to scientific articles. The pathway Chemical carcinogenesis is highly associated with colorectal cancer [68]. Phosphatidylinositol 3-Kinase is important in the management of metastatic colorectal cancer [69].…”

Section: The Usefulness Of the Combined Gene Weightmentioning

confidence: 99%

gwSPIA: Improved Signaling Pathway Impact Analysis With Gene Weights

Bao

Chen

et al. 2019

IEEE Access

View full text Add to dashboard Cite

Gene set analysis using signaling pathway has become a popular downstream analysis following differential expression analysis. From a biological point of view, only some portions of a pathway are expected to be altered; however, a few approaches using the different importance of genes in signaling pathways, which encompass the constitutive functional nonequivalent roles of genes in real pathways, have been proposed and none of them tries to associate the importance of genes with the related disease. In this paper, we developed an extended method of signaling pathway impact analysis (SPIA), called gwSPIA, by incorporating three signaling pathway-based gene weight merits that reflect the importance of genes from different aspects and attempt to associate the importance of genes with the related diseases. By applying the gwSPIA to the gene expression data sets in comparison with other seven methods in three measures, sensitivity, prioritization, and specificity, we show that the gwSPIA ranks in the second place in both sensitivity and prioritization. Furthermore, the specificity of the gwSPIA is better than SPIA, which is lower than 25%. The results also suggest that the gene weight used in the gwSPIA can reflect the association between the genes and the related diseases. The R package of the gwSPIA can be accessed from https://github.com/sterding/gwSPIA. INDEX TERMS Differentially expressed genes, gene weights, gwSPIA, signaling pathways analysis.

show abstract

The Role of Chemical Carcinogens and Their Biotransformation in Colorectal Cancer

Cited by 2 publications

References 84 publications

Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer

Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer

gwSPIA: Improved Signaling Pathway Impact Analysis With Gene Weights

Contact Info

Product

Resources

About