Effects of Black Raspberry on Dibenzo[a,l]Pyrene Diol Epoxide Induced DNAAdducts, Mutagenesis, and Tumorigenesis in the Mouse Oral Cavity

Kun Ming Chen, Joseph Guttenplan, Yuan Wan Sun, Timothy Cooper, Nora A.E. Shalaby, Wieslawa Kosinska, Gabrielle Benitez, Cesar Aliaga, Junjia Zhu, Jason Liao, Krishne Gowda, Shantu Amin, Gary Stoner, Karam El-Bayoumy

Research output: Contribution to journalArticle

Abstract

We previously showed that metabolic activation of the environmental and tobacco smoke constituent dibenzo[a,l]pyrene (DB[a,l]P) to its active fjord region diol epoxide (DB[a,l]PDE) is required to induce DNA damage, mutagenesis, and squamous cell carcinoma (SCC) in the mouse oral cavity. In contrast to procarcinogens, which were employed previously to induce SCC, DB[a,l]PDE does not requiremetabolic activation to exert its biological effects, and thus, this study was initiated to examine, for the first time, whether black raspberry powder (BRB) inhibits postmetabolic processes, such as DNA damage, mutagenesis, and tumorigenesis. Prior to long-term chemoprevention studies, we initially examined the effect of BRB (5% added to AIN-93M diet) on DNA damage in B6C3F1 mice using LC/MS-MS and on mutagenesis in the lacI gene in the mouse oral cavity. We showed that BRB inhibited DB[a,l]PDE-induced DNA damage (P < 0.05) and mutagenesis (P = 0.053) in the oral cavity. Tumor incidence in the oral cavity (oral mucosa and tongue) of mice fed diet containing 5% BRB was significantly (P < 0.05) reduced from 93% to 66%. Specifically, the incidence of benign tumor was significantly (P < 0.001) reduced from 90% to 31% (62% to 28% in the oral cavity and 28% to 2% in the tongue), a nonsignificant reduction of malignant tumors from 52% to 45%. Our preclinical findings demonstrate for the first time that the chemopreventive efficacy of BRB can be extended to direct-acting carcinogens that do not require phase I enzymes and is not just limited to procarcinogens.

Original languageEnglish (US)
Pages (from-to)157-164
Number of pages8
JournalCancer Prevention Research
Volume11
Issue number3
DOIs
StatePublished - Mar 1 2018

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Mutagenesis
Powders
Mouth
Carcinogenesis
DNA Damage
Tongue
Squamous Cell Carcinoma
Diet
Estuaries
Neoplasms
Epoxy Compounds
Incidence
Chemoprevention
Mouth Mucosa
Smoke
Carcinogens
Tobacco
Rubus
dibenzo(a,l)pyrene diol epoxide
Enzymes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Effects of Black Raspberry on Dibenzo[a,l]Pyrene Diol Epoxide Induced DNAAdducts, Mutagenesis, and Tumorigenesis in the Mouse Oral Cavity. / Chen, Kun Ming; Guttenplan, Joseph; Sun, Yuan Wan; Cooper, Timothy; Shalaby, Nora A.E.; Kosinska, Wieslawa; Benitez, Gabrielle; Aliaga, Cesar; Zhu, Junjia; Liao, Jason; Gowda, Krishne; Amin, Shantu; Stoner, Gary; El-Bayoumy, Karam.

In: Cancer Prevention Research, Vol. 11, No. 3, 01.03.2018, p. 157-164.

Research output: Contribution to journalArticle

Chen, KM, Guttenplan, J, Sun, YW, Cooper, T, Shalaby, NAE, Kosinska, W, Benitez, G, Aliaga, C, Zhu, J, Liao, J, Gowda, K, Amin, S, Stoner, G & El-Bayoumy, K 2018, 'Effects of Black Raspberry on Dibenzo[a,l]Pyrene Diol Epoxide Induced DNAAdducts, Mutagenesis, and Tumorigenesis in the Mouse Oral Cavity', Cancer Prevention Research, vol. 11, no. 3, pp. 157-164. https://doi.org/10.1158/1940-6207.CAPR-17-0278
Chen, Kun Ming ; Guttenplan, Joseph ; Sun, Yuan Wan ; Cooper, Timothy ; Shalaby, Nora A.E. ; Kosinska, Wieslawa ; Benitez, Gabrielle ; Aliaga, Cesar ; Zhu, Junjia ; Liao, Jason ; Gowda, Krishne ; Amin, Shantu ; Stoner, Gary ; El-Bayoumy, Karam. / Effects of Black Raspberry on Dibenzo[a,l]Pyrene Diol Epoxide Induced DNAAdducts, Mutagenesis, and Tumorigenesis in the Mouse Oral Cavity. In: Cancer Prevention Research. 2018 ; Vol. 11, No. 3. pp. 157-164.
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abstract = "We previously showed that metabolic activation of the environmental and tobacco smoke constituent dibenzo[a,l]pyrene (DB[a,l]P) to its active fjord region diol epoxide (DB[a,l]PDE) is required to induce DNA damage, mutagenesis, and squamous cell carcinoma (SCC) in the mouse oral cavity. In contrast to procarcinogens, which were employed previously to induce SCC, DB[a,l]PDE does not requiremetabolic activation to exert its biological effects, and thus, this study was initiated to examine, for the first time, whether black raspberry powder (BRB) inhibits postmetabolic processes, such as DNA damage, mutagenesis, and tumorigenesis. Prior to long-term chemoprevention studies, we initially examined the effect of BRB (5{\%} added to AIN-93M diet) on DNA damage in B6C3F1 mice using LC/MS-MS and on mutagenesis in the lacI gene in the mouse oral cavity. We showed that BRB inhibited DB[a,l]PDE-induced DNA damage (P < 0.05) and mutagenesis (P = 0.053) in the oral cavity. Tumor incidence in the oral cavity (oral mucosa and tongue) of mice fed diet containing 5{\%} BRB was significantly (P < 0.05) reduced from 93{\%} to 66{\%}. Specifically, the incidence of benign tumor was significantly (P < 0.001) reduced from 90{\%} to 31{\%} (62{\%} to 28{\%} in the oral cavity and 28{\%} to 2{\%} in the tongue), a nonsignificant reduction of malignant tumors from 52{\%} to 45{\%}. Our preclinical findings demonstrate for the first time that the chemopreventive efficacy of BRB can be extended to direct-acting carcinogens that do not require phase I enzymes and is not just limited to procarcinogens.",
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