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Benzo(a)pyrene-induced cytotoxicity, cell proliferation, DNA damage, and altered gene expression profiles in HT-29 human colon cancer cells

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Abstract

In the US alone, around 60,000 lives/year are lost to colon cancer. In order to study the mechanisms of colon carcinogenesis, in vitro model systems are required in addition to in vivo models. Towards this end, we have used the HT-29 colon cancer cells, cultured in Dulbecco’s Modified Eagle Medium (DMEM), which were exposed to benzo(a)pyrene (BaP), a ubiquitous and prototypical environmental and dietary toxicant at 1, 10, 100 nM and 1, 5, 10, and 25 μM concentrations for 96 h. Post-BaP exposure, growth, cytotoxicity, apoptosis, and cell cycle changes were determined. The BaP metabolite concentrations in colon cells were identified and measured. Furthermore, the BaP biotransformation enzymes were studied at the protein and mRNA levels. The BaP exposure–induced damage to DNA was assessed by measuring the oxidative damage to DNA and the concentrations of BaP-DNA adducts. To determine the whole repertoire of genes that are up- or downregulated by BaP exposure, mRNA transcriptome analysis was conducted. There was a BaP exposure concentration (dose)-dependent decrease in cell growth, cytotoxicity, and modulation of the cell cycle in the treatment groups compared to untreated or dimethylsulfoxide (DMSO: vehicle for BaP)-treated categories. The phase I biotransformation enzymes, CYP1A1 and 1B1, showed BaP concentration-dependent expression. On the other hand, phase II enzymes did not exhibit any marked variation. Consistent with the expression of phase I enzymes, elevated concentrations of BaP metabolites were generated, contributing to the formation of DNA lesions and stable DNA adducts, which were also BaP concentration-dependent. In summary, our studies established that biotransformation of BaP contributes to cytotoxicity, proliferation of tumor cells, and alteration of gene expression by BaP.

Graphical abstract

• Benzo(a)pyrene (BaP) is an environmental and dietary toxicant.

• BaP causes cytotoxicity in cultured HT-29 colon cancer cells.

• mRNA transcriptome analyses revealed that BaP impacts cell growth, cell cycle, biotransformation, and DNA damage.

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References

  • Ajayi BO, Adedara IA, Farombi EO. Benzo(a)pyrene induces oxidative stress, pro- inflammatory cytokines, expression of nuclear factor-kappa B and deregulation of wnt/beta-catenin signaling in colons of BALB/c mice. Food Chem Toxicol. 2016;95:42–51.

    CAS  PubMed  Google Scholar 

  • Almahmeed T, Boyle JO, Cohen EG, Carew JF, Du B, Altorki NK, et al. Benzo[a]pyrene phenols are more potent inducers of CYP1A1, CYP1B1 and COX-2 than benzo[a]pyrene glucuronides in cell lines derived from the human aerodigestive tract. Carcinogenesis. 2004;25(5):793–9.

    CAS  PubMed  Google Scholar 

  • Banks LD, Amoah P, Niaz MS, Washington MK, Adunyah SE, Ramesh A. Olive oil prevents benzo(a)pyrene [B(a)P]-induced colon carcinogenesis through altered B(a)P metabolism and decreased oxidative damage in ApcMin mouse model. J Nutr Biochem. 2016;28:37–50.

    CAS  PubMed  Google Scholar 

  • Bolton JL, Trush MA, Penning TM, Dryhurst G, Monks TJ. Role of quinones in toxicology. Chem Res Toxicol. 2000;13:135–60.

    CAS  PubMed  Google Scholar 

  • Bothe H, Götz C, Stobbe-Maicherski N, Fritsche E, Abel J, Haarmann-Stemmann T. Luteolin enhances the bioavailability of benzo(a)pyrene in human colon carcinoma cells. Arch Biochem Biophys. 2010;498(2):111–8.

    CAS  PubMed  Google Scholar 

  • Buesen R, Mock M, Seidel A, Jacob J, Lampen A. Interaction between metabolism and transport of benzo[a]pyrene and its metabolites in enterocytes. Toxicol Appl Pharmacol. 2002;183:168–78.

    CAS  PubMed  Google Scholar 

  • Burdick AD, Davis JW 2nd, Liu KJ, Hudson LG, Shi H, Monske ML, et al. Benzo(a)pyrene quinones increase cell proliferation, generate reactive oxygen species and transactivate the epidermal growth factor receptor in breast epithelial cells. Cancer Res. 2003;63:7825–33.

    CAS  PubMed  Google Scholar 

  • Cao D, Yoon CH, Shin BS, Kim CH, Park ES, Yoo SD. Effects of aloe, aloesin, or propolis on the pharmacokinetics of benzo[a]pyrene and 3-OH-benzo[a]pyrene in rats. J Toxicol Environ Health A. 2005;68(23–24):2227–38.

    CAS  PubMed  Google Scholar 

  • Cavalieri EL, Rogan EG. Central role of radical cations in metabolic activation of polycyclic aromatic hydrocarbons. Xenobiotica. 1995;25:677–88.

    CAS  PubMed  Google Scholar 

  • Cavalieri EL, Rogan E. The primary role of apurinic sites in tumor initiation. Polycycl Aromat Compd. 1996;10:1–4.

    Google Scholar 

  • Chakravarti D, Pelling JC, Cavalieri EL, Rogan EG. Relating aromatic hydrocarbon-induced DNA adducts and c-H-ras mutations in mouse skin papillomas: the role of apurinic sites. Proc Natl Acad Sci U S A. 1995;92:10422–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen L, Devanesan PD, Higginbotham S, Ariese F, Jankowiak R, Small GJ, et al. Expanded analysis of benzo[a]pyrene-DNA adducts formed in vitro and in mouse skin: their significance in tumor initiation. Chem Res Toxicol. 1996;9:897–903.

    CAS  PubMed  Google Scholar 

  • Chramostová K, Vondrácek J, Sindlerová L, Vojtesek B, Kozubík A, Machala M. Polycyclic aromatic hydrocarbons modulate cell proliferation in rat hepatic epithelial stem-like WB-F344 cells. Toxicol Appl Pharmacol. 2004;196:136–48.

    PubMed  Google Scholar 

  • Darwish WS, Chiba H, El-Ghareeb WR, Elhelaly AE, Hui SP. Determination of polycyclic aromatic hydrocarbon content in heat-treated meat retailed in Egypt: health risk assessment, benzo[a]pyrene induced mutagenicity and oxidative stress in human colon (CaCo-2) cells and protection using rosmarinic and ascorbic acids. Food Chem. 2019;30:114–24.

    Google Scholar 

  • de Waard WJ, Aarts JMMJG, Peijnenburg AACM, Baykus H, Talsma E, Punt A, et al. Gene expression profiling in Caco-2 human colon cells exposed to TCDD, benzo(a)pyrene, and natural Ah receptor agonists from cruciferous vegetables and citrus fruits. Toxicol in Vitro. 2008;22:396–410.

    PubMed  Google Scholar 

  • Diggs DL, Myers JN, Banks LD, Niaz MS, Hood DB, Roberts LJ, et al. Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer. J Nutr Biochem. 2013;24:2051–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Domingo JL, Nadal M. Human dietary exposure to polycyclic aromatic hydrocarbons: a review of the scientific literature. Food Chem Toxicol. 2015;86:144–53.

    CAS  PubMed  Google Scholar 

  • Earnshaw WC, Martins LM, Kaufmann SH. Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem. 1999;68:383–424.

    CAS  PubMed  Google Scholar 

  • Ebert MN, Klinder A, Peters WHM, Schaferhenrich A, Sendt W, Scheele J, et al. Expression of glutathione S-transferases (GSTs) in human colon cells and inducibility of GSTM2 by butyrate. Carcinogenesis. 2003;24:1637–44.

    CAS  PubMed  Google Scholar 

  • Foth H, Kahl R, Kahl GF. Pharmacokinetics of low doses of benzo[a]pyrene in the rat. Food Chem Toxicol. 1988;26(1):45–51.

    CAS  PubMed  Google Scholar 

  • Friedman E, Urmacher C, Winawer S. A model for human colon carcinoma evolution based on the differential response of cultured preneoplastic, premalignant, and malignant cells to 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 1984;44:1568–78.

    CAS  PubMed  Google Scholar 

  • Galván N, Teske DE, Zhou G, Moorthy B, MacWilliams PS, Czuprynski CJ, et al. Induction of CYP1A1 and CYP1B1 in liver and lung by benzo(a)pyrene and 7,12-d imethylbenz(a)anthracene do not affect distribution of polycyclic hydrocarbons to target tissue: role of AhR and CYP1B1 in bone marrow cytotoxicity. Toxicol Appl Pharmacol. 2005;202:244–57.

    PubMed  Google Scholar 

  • Guengerich FP. Forging the links between metabolism and carcinogenesis. Mutat Res. 2001;488:195–209.

    CAS  PubMed  Google Scholar 

  • Gupta RC, Randerath K. Analysis of DNA adducts by 32P labeling and thin layer chromatography. In: Friedberg EC, Hanawalt PC, editors. DNA Repair, vol. 3: Marcel Dekker, Inc; 1988. p. 399–418.

  • Harris KL, Banks LD, Mantey JA, Huderson AC, Ramesh A. Bioaccessibility of polycyclic aromatic hydrocarbons: relevance to toxicity and carcinogenesis. Expert Opin Drug Metab Toxicol. 2013;9(11):1465–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Harris KL, Pulliam SR, Okoro E, Guo Z, Washington MK, Adunyah SE, et al. Western diet enhances benzo(a)pyrene-induced colon tumorigenesis in a polyposis in rat coli (PIRC) rat model of colon cancer. Oncotarget. 2016;7:28947–60.

    PubMed  PubMed Central  Google Scholar 

  • Heredia-Ortiz R, Bouchard M. Understanding the linked kinetics of benzo(a)pyrene and 3-hydroxybenzo(a)pyrene biomarker of exposure using physiologically-based pharmacokinetic modelling in rats. J Pharmacokinet Pharmacodyn. 2013;40:669–82.

    CAS  PubMed  Google Scholar 

  • Higgins TJ, Bailey PJ, Allsopp D, Imhof DA. Cultured neonate rat myocytes as a model for the study of myocardial ischaemic necrosis. J Pharm Pharmacol. 1981;33:644–9.

    CAS  PubMed  Google Scholar 

  • Hockley SL, Arlt VM, Jahnke G, Hartwig A, Giddings I, Phillips DH. Identification through microarray gene expression analysis of cellular responses to benzo(a)pyrene and its diol-epoxide that are dependent or independent of p53. Carcinogenesis. 2008;29:202–10.

    CAS  PubMed  Google Scholar 

  • Huderson AC, Rekha Devi PV, Niaz MS, Adunyah SE, Ramesh A. Alteration of benzo(a)pyrene biotransformation by resveratrol in ApcMin/+ mouse model of colon carcinogenesis. Investig New Drugs. 2019;37:238–51.

    CAS  Google Scholar 

  • Hummel JM, Madeen EP, Siddens LK, Uesugi SL, McQuistan T, Anderson KA, et al. Pharmacokinetics of [14C]-Benzo[a]pyrene (BaP) in humans: impact of co-administration of smoked salmon and BaP dietary restriction. Food Chem Toxicol. 2018;115:136–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Iwanari M, Nakajima M, Kizu R, Hayakawa K, Yokoi T. Induction of CYP1A1, CYP1A2, and CYP1B1 mRNAs by nitropolycyclic aromatic hydrocarbons in various human tissue-derived cells: chemical-cytochrome P450 isoform-, and cell-specific differences. Arch Toxicol. 2002;76:287–98.

    CAS  PubMed  Google Scholar 

  • Kabátková M, Zapletal O, Tylichová Z, Neča J, Machala M, Milcová A, et al. Inhibition of β-catenin signalling promotes DNA damage elicited by benzo[a]pyrene in a model of human colon cancer cells via CYP1 deregulation. Mutagenesis. 2015;30:565–76.

    PubMed  Google Scholar 

  • Khan QA, Anderson LM. Hydrocarbon carcinogens evade cellular defense mechanism of G1 arrest in nontransformed and malignant lung cell lines. Toxicol Appl Pharmacol. 2001;173:105–13.

    CAS  PubMed  Google Scholar 

  • Lampen A, Bader A, Bestmann T, Winklers M, Witte L, Borlak JT. Catalytic activities, protein-and mRNA-expression of cytochrome P450 isoenzymes in intestinal cell lines. Xenobiotica. 1998;28:429–41.

    CAS  PubMed  Google Scholar 

  • Liao Y, Wang J, Jaehnig EJ, Shi Z, Zhang B. WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res. 2019;47(W1):W199–205.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liévin-Le Moal V, Servin AL. Pathogenesis of human enterovirulent bacteria: lessons from cultured, fully differentiated human colon cancer cell lines. Microbiol Mol Biol Rev. 2013;77:380–439.

    PubMed  PubMed Central  Google Scholar 

  • Lin T, Yang MS. Benzo[a]pyrene-induced necrosis in the HepG(2) cells via PARP-1 activation and NAD(+) depletion. Toxicology. 2008;245:147–53.

    CAS  PubMed  Google Scholar 

  • Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis. 2000;21:485–95.

    CAS  PubMed  Google Scholar 

  • Luch A, Baird WM. Metabolic activation and detoxification of polycyclic aromatic hydrocarbons. In: Luch A, editor. The carcinogenic effects of polycyclic aromatic hydrocarbons. London: Imperial College Press; 2005. p. 19–96.

    Google Scholar 

  • Madeen E, Siddens LK, Uesugi S, McQuistan T, Corley RA, Smith J, et al. Toxicokinetics of benzo[a]pyrene in humans: extensive metabolism as determined by UPLC-accelerator mass spectrometry following oral micro-dosing. Toxicol Appl Pharmacol. 2019;364:97–105.

    CAS  PubMed  Google Scholar 

  • Marian B. In vitro models for the identification and characterization of tumor-promoting and protective factors for colon carcinogenesis. Food Chem Toxicol. 2002;40:1099–104.

    CAS  PubMed  Google Scholar 

  • Melendez-Colon VJ, Luch A, Seidel A, Baird WM. Formation of stable DNA adducts and apurinic sites upon metabolic activation of bay and fjord region polycyclic aromatic hydrocarbons in human cell cultures. Chem Res Toxicol. 2000;13:10–7.

    CAS  PubMed  Google Scholar 

  • Mitchell DM, Ball JM. Characterization of a spontaneously polarizing HT-29 cell line, HT-29/c/f8. Invitro Cell Dev Biol-Animal. 2004;40:297–302.

    Google Scholar 

  • Myers JN, Rekhadevi PV, Ramesh A. Comparative evaluation of different cell lysis and extraction methods for studying benzo(a)pyrene metabolism in HT-29 colon cancer cell cultures. Cell Physiol Biochem. 2011;28:209–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nicotera P, Leist M, Ferrando-May E. Apoptosis and necrosis: different execution of the same death. Biochem Soc Symp. 1999;66:69–73.

    CAS  PubMed  Google Scholar 

  • Niestroy J, Barbara A, Herbst K, Rode S, van Liempt M, Roos PH. Single and concerted effects of benzo[a]pyrene and flavonoids on the AhR and Nrf2-pathway in the human colon carcinoma cell line Caco-2. Toxicol in Vitro. 2011;25:671–83.

    CAS  PubMed  Google Scholar 

  • NIH guidelines for the laboratory use of chemical carcinogens. NIH Publication No. 81–2385. Washington, DC: U.S. Government Printing Office; 1981.

    Google Scholar 

  • Ohnishi S, Kawanishi S. Double base lesions of DNA by a metabolite of carcinogenic benzo[a]pyrene. Biochem Biophys Res Commun. 2002;290:778–82.

    CAS  PubMed  Google Scholar 

  • Ramesh A, Knuckles ME. Dose-dependent benzo(a)pyrene [B(a)P]-DNA adduct levels and persistence in F-344 rats following subchronic dietary exposure to B(a)P. Cancer Lett. 2006;240:268–78.

    CAS  PubMed  Google Scholar 

  • Ramesh A, Inyang F, Hood DB, Archibong AE, Knuckles ME, Nyanda AM. Metabolism, bioavailability, and toxicokinetics of benzo(a)pyrene in F344 rats following oral administration. Exp Toxic Pathol. 2001;53:275–90.

    CAS  Google Scholar 

  • Ramesh A, Walker SA, Hood DB, Guillén MD, Schneider K, Weyand EH. Bioavailability and risk assessment of orally ingested polycyclic aromatic hydrocarbons. Int J Toxicol. 2004;23:301–33.

    CAS  PubMed  Google Scholar 

  • Ramesh A, Archibong AE, Hood DB, Guo Z, Loganathan BG. Global environmental distribution and human health effects of polycyclic aromatic hydrocarbons. In: Loganathan BG, Lam PK-S, editors. Global contamination trends of persistent organic chemicals. Boca Raton, Florida: CRC Press; 2011. p. 95–124.

    Google Scholar 

  • Ramesh A, Archibong AE, Huderson AC, Diggs DL, Myers JN, Hood DB, et al. Polycyclic aromatic hydrocarbons. In: Gupta RC, editor. Veterinary toxicology. 2nd ed. London, UK: Academic Press; 2012.

    Google Scholar 

  • Ramzy GM, Koessler T, Ducrey E, McKee T, Ris F, Buchs N, et al. Patient-derived in vitro models for drug discovery in colorectal carcinoma. Cancers (Basel). 2020 May 31;12(6):1423.

    CAS  Google Scholar 

  • Reiners JJ Jr, Herlick S. Cell-cell proximity is a parameter affecting the transfer of mutagenic polycyclic aromatic hydrocarbons between cells. Carcinogenesis. 1985;6:793–5.

    CAS  PubMed  Google Scholar 

  • Rosenberg DW, Leff T. Regulation of cytochrome P450 in cultured human colonic cells. Arch Biochem Biophys. 1993;300:186–92.

    CAS  PubMed  Google Scholar 

  • Sambruy Y, Ferruzza S, Ranaldi G. DeAngelis I: Intestinal cell culture models. Applications in toxicology and pharmacology. Cell Biol Toxicol. 2001;17:301–17.

    CAS  PubMed  Google Scholar 

  • Schroeder A, Mueller O, Stocker S, Salowsky R, Leiber M, Gassmann M, et al. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol. 2006;31(7):3.

    Google Scholar 

  • Shimada T, Inoue K, Suzuki Y, Kawai T, Azuma E, Nakajima T, et al. Arylhydrocarbon receptor-dependent induction of liver and lung cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in genetically engineered C57BL/6J mice. Carcinogenesis. 2002;23:1199–207.

    CAS  PubMed  Google Scholar 

  • Shimada T, Guengerich FP. Inhibition of human cytochrome P450 1A1-, 1A2-, and 1B1-mediated activation of procarcinogens to genotoxic metabolites by polycyclic aromatic hydrocarbons. Chem Res Toxicol. 2006;19:288–94.

    CAS  PubMed  Google Scholar 

  • Shimada T, Hayes CL, Yamazaki H, Amin S, Hecht SS, Guengerich FP, et al. Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1. Cancer Res. 1996;56:2979–84.

    CAS  PubMed  Google Scholar 

  • Shimada T, Yamazaki H, Foroozesh M, Hopkins NE, Alworth WL, Guengerich FP. Selectivity of polycyclic inhibitors for human cytochrome P450s 1A1, 1A2, and 1B1. Chem Res Toxicol. 1998;11:1048–56.

    CAS  PubMed  Google Scholar 

  • Shimada T, Gillam EM, Oda Y, Tsumura F, Sutter TR, Guengerich FP, et al. Metabolism of benzo[a]pyrene to trans-7,8-dihydroxy-7, 8-dihydrobenzo[a]pyrene by recombinant human cytochrome P450 1B1 and purified liver epoxide hydrolase. Chem Res Toxicol. 1999;12:623–9.

    CAS  PubMed  Google Scholar 

  • Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020 Mar 5;70:145–64. https://doi.org/10.3322/caac.21601.

    Article  PubMed  Google Scholar 

  • Sonoda J, Seki Y, Hakura A, Hosokawa S. Time course of the incidence/multiplicity and histopathological features of murine colonic dysplasia, adenoma and adenocarcinoma induced by benzo[a]pyrene and dextran sulfate sodium. J Toxicol Pathol. 2015;28:109–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sun N, Panetta NJ, Gupta DM, Wilson KD, Lee A, Jia F, et al. Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells. Proc Natl Acad Sci U S A. 2009;106:15720–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tait SW, Ichim G, Green DR. Die another way--non-apoptotic mechanism of cell death. J Cell Sci. 2014;127:2135–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tannheimer SL, Ethier SP, Caldwell KK, Burchiel SW. Benzo[a]pyrene- and TCDD-induced alterations in tyrosine phosphorylation and insulin-like growth factor signaling pathways in the MCF-10A human mammary epithelial cell line. Carcinogenesis. 1998;19:1291–7.

    CAS  PubMed  Google Scholar 

  • Tarantini A, Maitre A, Lefebvre E, Marques M, Marie C, Ravanat JL, et al. Relative contribution of DNA strand breaks and DNA adducts to the genotoxicity of benzo[a]pyrene as a pure compound and in complex mixtures. Mutat Res. 2009;671:67–75.

    CAS  PubMed  Google Scholar 

  • Testa U, Pelosi E, Castelli G. Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells. Med Sci (Basel). 2018;6:31.

    Google Scholar 

  • Tylichová Z, Neča J, Topinka J, Milcová A, Hofmanová J, Kozubík A, et al. n-3 Polyunsaturated fatty acids alter benzo[a]pyrene metabolism and genotoxicity in human colon epithelial cell models. Food Chem Toxicol. 2019;124:374–84.

    PubMed  Google Scholar 

  • Udoko AN, Johnson CA, Dykan A, Rachakonda G, Villalta F, Mandape SN, et al. Early regulation of profibrotic genes in primary human cardiac myocytes by Trypanosoma cruzi. PLoS Negl Trop Dis. 2016;10(1):e0003747.

    PubMed  PubMed Central  Google Scholar 

  • Veith A, Moorthy B. Role of cytochrome P450s in the generation and metabolism of reactive oxygen species. Curr Opin Toxicol. 2018;7:44–51.

    PubMed  Google Scholar 

  • Willis AJ, Indra R, Wohak LE, Sozeri O, Feser K, Mrizova I, et al. The impact of chemotherapeutic drugs on the CYP1A1-catalysed metabolism of the environmental carcinogen benzo[a]pyrene: effects in human colorectal HCT116 TP53(+/+), TP53(+/−) and TP53(−/−) cells. Toxicology. 2018:398–9.

  • Wohak LE, Krais AM, Kucab JE, Stertmann J, Øvrebø S, Seidel A, et al. Carcinogenic polycyclic aromatic hydrocarbons induce CYP1A1 in human cells via a p53-dependent mechanism. Arch Toxicol. 2016;90:291–304.

    CAS  PubMed  Google Scholar 

  • Xie Y, Lu W, Liu S, Yang Q, Goodwin JS, Sathyanarayana SA, et al. MMP7 interacts with ARF in nucleus to potentiate tumor microenvironments for prostate cancer progression in vivo. Oncotarget. 2016;7:47609–19.

    PubMed  PubMed Central  Google Scholar 

  • Yuan L, Liu J, Deng H, Gao C. Benzo[a]pyrene induces autophagic and pyroptotic death simultaneously in HL-7702 human normal liver cells. J Agric Food Chem. 2017;65:9763–73.

    CAS  PubMed  Google Scholar 

  • Zapletal O, Tylichová Z, Neča J, Kohoutek J, Machala M, Milcová A, et al. Butyrate alters expression of cytochrome P450 1A1 and metabolism of benzo[a]pyrene via its histone deacetylase activity in colon epithelial cell models. Arch Toxicol. 2017;91:2135–50.

    CAS  PubMed  Google Scholar 

  • Zapletal O, Procházková J, Dubec V, Hofmanová J, Kozubík A, Vondráček J. Butyrate interacts with benzo[a]pyrene to alter expression and activities of xenobiotic metabolizing enzymes involved in metabolism of carcinogens within colon epithelial cell models. Toxicology. 2019;412:1–11.

    CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to acknowledge the award of Dissertation Research Fellowships by the Southern Regional Education Board, Atlanta, GA (JNM and KLH), and Middle Tennessee State University, Murfreesboro (JNM). Technical support from Ms. Qiujia Shao is also acknowledged.

Author contribution statement

Jeremy Myers: Overall study design, methodology, investigation, data analysis, and writing—original draft preparation. Kelly Harris: Cell cycle study design, methodology, data analysis, and input into manuscript preparation. Perumalla Rekhadevi: DNA damage study design, data analysis, and input into manuscript preparation. Siddharth Pratap: Bioinformatics study design, data analysis, and input into manuscript preparation. Aramandla Ramesh: Conceptualization, methodology, data curation, project administration, funding acquisition, supervision, and writing—review and editing.

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This research was funded by the National Institutes of Health (NIH) grants 5R01CA142845-04, 5R25GM059994-11, G12RR003032, 5T32HL007735-12, G12MD007586-29, and 5U54CA163069-04 and the EPA STAR grant G17D112354237.

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  1. Department of Biochemistry, Cancer Biology, Neuroscience & Pharmacology, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, TN, 37208, USA

    Jeremy N. Myers, Kelly L. Harris & Aramandla Ramesh

  2. Department of Biotechnology, St. Francis College for Women, Hyderabad, Telangana, 500016, India

    Perumalla V. Rekhadevi

  3. School of Graduate Studies, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, TN, 37208, USA

    Siddharth Pratap

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Myers, J.N., Harris, K.L., Rekhadevi, P.V. et al. Benzo(a)pyrene-induced cytotoxicity, cell proliferation, DNA damage, and altered gene expression profiles in HT-29 human colon cancer cells. Cell Biol Toxicol 37, 891–913 (2021). https://doi.org/10.1007/s10565-020-09579-5

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