Tissue-Specific Attenuation of Endogenous DNA I-Compounds in Rats by Carcinogen Azoxymethane: Possible Role of Dietary Fish Oil in Colon Cancer Prevention

Zhou, Guodong; Popović, Nataša; Lupton, Joannè R.; Turner, Nancy D.; Chapkin, Robert S.; Donnelly, Kirby C.

doi:10.1158/1055-9965.epi-04-0759

Cited by 10 publications

(11 citation statements)

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“…78 Fish oil reduces proliferation in upper-crypt cells of patients with a history of colonic polyps, 79 inhibits colon tumors, 80 in combination with fiber reduces aberrant crypt foci formation, 81 and has chemopreventive effects in colon cancer. 82 Whey suppresses angiogenesis and tumor development and induces apoptosis. 83 Shark cartilage is antiangiogenic, 84 although 1 human study found no benefits.…”

Section: Discussionmentioning

confidence: 99%

Colon Cancer Survival With Herbal Medicine and Vitamins Combined With Standard Therapy in a Whole-Systems Approach

et al. 2011

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Although localized colon cancer is often successfully treated with surgery, advanced disease requires aggressive systemic therapy that has lower effectiveness. Approximately 30% to 75% of patients with colon cancer use complementary and alternative medicine (CAM), but there is limited formal evidence of survival efficacy. In a consecutive case series with 10-year follow-up of all colon cancer patients (n = 193) presenting at a San Francisco Bay-Area center for Chinese medicine (Pine Street Clinic, San Anselmo, CA), the authors compared survival in patients choosing short-term treatment lasting the duration of chemotherapy/radiotherapy with those continuing long-term. To put these data into the context of treatment responses seen in conventional medical practice, they also compared survival with Pan-Asian medicine + vitamins (PAM+V) with that of concurrent external controls from Kaiser Permanente Northern California and California Cancer Registries. Kaplan-Meier, traditional Cox regression, and more modern methods were used for causal inference—namely, propensity score and marginal structural models (MSMs), which have not been used before in studies of cancer survival and Chinese herbal medicine. PAM+V combined with conventional therapy, compared with conventional therapy alone, reduced the risk of death in stage I by 95%, stage II by 64%, stage III by 29%, and stage IV by 75%. There was no significant difference between short-term and long-term PAM+V. Combining PAM+V with conventional therapy improved survival, compared with conventional therapy alone, suggesting that prospective trials combining PAM+V with conventional therapy are justified.

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Section: Discussionmentioning

confidence: 99%

Colon Cancer Survival With Herbal Medicine and Vitamins Combined With Standard Therapy in a Whole-Systems Approach

et al. 2011

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“…The fatty acid compositions of FO and CO are listed in Table 2. In order to meet essential fatty acid requirements, the FO diet contained 3.5 g of corn oil/100 g of diet [31], [32]. To prevent formation of oxidized lipids, the diet was stored at −20°C in the dark.…”

Section: Methodsmentioning

confidence: 99%

“…DNA extraction and 32 P-postlabeling analyses were performed as in previous experiments [32]. DNA was isolated by solvent extraction combined with enzymatic digestion of protein and RNA [26], [27] and stored at −80°C until analysis.…”

Section: Methodsmentioning

confidence: 99%

Effects of Dietary Fish Oil on the Depletion of Carcinogenic PAH-DNA Adduct Levels in the Liver of B6C3F1 Mouse

Zhou

Zhu²,

Phillips

et al. 2011

PLoS ONE

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Many carcinogenic polycyclic aromatic hydrocarbons (PAHs) and their metabolites can bind covalently to DNA. Carcinogen-DNA adducts may lead to mutations in critical genes, eventually leading to cancer. In this study we report that fish oil (FO) blocks the formation of DNA adducts by detoxification of PAHs. B6C3F1 male mice were fed a FO or corn oil (CO) diet for 30 days. The animals were then treated with seven carcinogenic PAHs including benzo(a)pyrene (BaP) with one of two doses via a single intraperitoneal injection. Animals were terminated at 1, 3, or 7 d after treatment. The levels of DNA adducts were analyzed by the 32P-postlabeling assay. Our results showed that the levels of total hepatic DNA adducts were significantly decreased in FO groups compared to CO groups with an exception of low PAH dose at 3 d (P = 0.067). Total adduct levels in the high dose PAH groups were 41.36±6.48 (Mean±SEM) and 78.72±8.03 in 109 nucleotides (P = 0.011), respectively, for the FO and CO groups at 7 d. Animals treated with the low dose (2.5 fold lower) PAHs displayed similar trends. Total adduct levels were 12.21±2.33 in the FO group and 24.07±1.99 in the CO group, P = 0.008. BPDE-dG adduct values at 7 d after treatment of high dose PAHs were 32.34±1.94 (CO group) and 21.82±3.37 (FO group) in 109 nucleotides with P value being 0.035. Low dose groups showed similar trends for BPDE-dG adduct in the two diet groups. FO significantly enhanced gene expression of Cyp1a1 in both the high and low dose PAH groups. Gstt1 at low dose of PAHs showed high levels in FO compared to CO groups with P values being 0.014. Histological observations indicated that FO played a hepatoprotective role during the early stages. Our results suggest that FO has a potential to be developed as a cancer chemopreventive agent.

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“…DNA extraction and 32 P-postlabeling analyses were performed as in previous experiments (Phillips and Arlt 2007; Zhou et al 2005). DNA was isolated by solvent extraction combined with enzymatic digestion of protein and RNA (Gupta 1984; Randerath et al 1981) and stored at –80°C until analysis.…”

Section: Methodsmentioning

confidence: 99%

Mechanistic relationships between hepatic genotoxicity and carcinogenicity in male B6C3F1 mice treated with polycyclic aromatic hydrocarbon mixtures

et al. 2014

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The genotoxicity of a complex mixture [neutral fraction (NF)] from a wood preserving waste and reconstituted mixture (RM) mimicking the NF with seven major polycyclic aromatic hydrocarbons (PAHs) and benzo(a)pyrene (BaP) was investigated by determining DNA adducts and tumor incidence in male B6C3F1 mice exposed to 3 different doses of the chemical mixtures. The peak values of DNA adducts were observed after 24 h and the highest levels of PAH-DNA adducts were exhibited in mice administered NF+BaP, and the highest tumor incidence and mortality were also observed in this group. DNA adduct levels after 1, 7, or 21 d were significantly correlated with animal mortality and incidence of total tumors including liver, lung, and forestomach. However, only hepatic DNA adducts after 7 d significantly correlated with liver tumor incidence. Most proteins involved in DNA repair including ATM, pATR, Chk1, pChk1, DNA PKcs, XRCC1, FANCD2, Ku80, Mre11 and Brca2 were significantly lower in liver tumor tissue compared to non-tumor tissue. Expression of proteins involved in apoptosis and cell cycle regulation were also significantly different in tumor vs non-tumor tissues and it is possible that PAH-induced changes in these gene products are important for tumor development and growth.

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Tissue-Specific Attenuation of Endogenous DNA I-Compounds in Rats by Carcinogen Azoxymethane: Possible Role of Dietary Fish Oil in Colon Cancer Prevention

Abstract: I-compounds are bulky covalent DNA modifications that are derived from metabolic intermediates of nutrients. Some

Cited by 10 publications

References 64 publications

Colon Cancer Survival With Herbal Medicine and Vitamins Combined With Standard Therapy in a Whole-Systems Approach

Colon Cancer Survival With Herbal Medicine and Vitamins Combined With Standard Therapy in a Whole-Systems Approach

Effects of Dietary Fish Oil on the Depletion of Carcinogenic PAH-DNA Adduct Levels in the Liver of B6C3F1 Mouse

Mechanistic relationships between hepatic genotoxicity and carcinogenicity in male B6C3F1 mice treated with polycyclic aromatic hydrocarbon mixtures

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