Etheno-DNA adduct formation in rats gavaged with linoleic acid, oleic acid and coconut oil is organ- and gender specific

Fang, Qingming; Nair, Jagadeesan; Sun, Xin; Hadjiolov, D.; Bartsch, Helmut

doi:10.1016/j.mrfmmm.2007.04.002

Cited by 13 publications

(8 citation statements)

References 39 publications

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“…18 Etheno-DNA adducts in LA-treated female rats were found to be 8-13 times higher in WBC when compared with males. 18,19 Females seemed to be more susceptible to LPO-induced DNA damage, possibly as a consequence of interaction of x-6 PUFA with 4-hydroxylated estradiol metabolites which may undergo redox-cycling ( Fig. 1), thereby producing reactive oxygen species and increasing LPO of membrane fatty acids as proposed earlier.…”

mentioning

confidence: 59%

“…The reaction was performed in 1.5 ml glass vials with screw caps under argon gas. 19 The incubation mixture typically contained 40 lg purified calf thymus DNA (CT-DNA), 20 lM substrate (2-/ 4-OH-E 2 ) and 50 lM of arachidonic acid in a 100 ll PBS buffer pH 7.0. After shaking at 37 C for 6 hr, the DNA was precipitated by adding 0.1 vol.…”

Section: In Vitro Assay For the Formation Of Dna Adductsmentioning

confidence: 99%

“…Male and female rats were gavaged with LA (ω‐6 PUFA), OA (MUFA), or coconut oil (saturated fatty acids) 18. Etheno‐DNA adducts in LA‐treated female rats were found to be 8–13 times higher in WBC when compared with males 18, 19. Females seemed to be more susceptible to LPO‐induced DNA damage, possibly as a consequence of interaction of ω‐6 PUFA with 4‐hydroxylated estradiol metabolites which may undergo redox‐cycling (Fig.…”

mentioning

confidence: 97%

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Lipid peroxidation and DNA adduct formation in lymphocytes of premenopausal women: Role of estrogen metabolites and fatty acid intake

Sun

Nair

Linseisen

et al. 2012

Intl Journal of Cancer

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A diet high in linoleic acid (an x-6 PUFA) increased the formation of miscoding etheno (e) -DNA adducts in WBC-DNA of women, but not in men (Nair et al., Cancer Epidemiol Biomark Prev 1997;6:597-601). This gender specificity could result from an interaction between x-6 PUFA intake and estrogen catabolism, via redox-cycling of 4-hydroxyestradiol (4-OH-E 2 ) and subsequent lipid peroxidation (LPO). In this study, we investigated whether in premenopausal women LPO-derived adducts in WBC-DNA are affected by serum concentration of 2-and 4-hydroxyestradiol metabolites and by fatty acid intake. DNA extracted from buffy coat and plasma samples, both blindly coded from healthy women (N 5 124, median age 40 year) participating in the EPIC-Heidelberg cohort study were analyzed. Three LPO-derived exocyclic DNA adducts, edA, edC and M 1 dG were quantified by immuno-enriched 32 P-postlabelling and estradiol metabolites by ultra-sensitive GC-mass spectrometry. Mean M 1 dG levels in WBC-DNA were distinctly higher than those of edA and edC, and all were positively and significantly interrelated. Serum levels of 4-OH-E 2 , but not of 2-OH-E 2 , metabolites were positively related to etheno DNA adduct formation. Positive correlations existed between M 1 dG levels and linoleic acid intake or the ratios of dietary linoleic acid/oleic acid and PUFA/MUFA. Aerobic incubation of 4-OH-E 2 , arachidonic acid and calf thymus DNA yielded two to threefold higher etheno DNA adduct levels when compared with assays containing 2-OH-E 2 instead. In conclusion, this study is the first to compare M 1 dG and etheno-DNA adducts and serum estradiol metabolites in human samples in the same subjects. Our results support a novel mechanistic link between estradiol catabolism, dietary x-6 fatty acid intake and LPO-induced DNA damage supported by an in vitro model. Similar studies in human breast epithelial tissue and on amplification of DNA-damage in breast cancer patients are in progress.Persistent cellular oxidative stress and enhanced lipid peroxidation (LPO), leading to macromolecular damage and disruption of signaling pathways are implicated in the development of human malignancies.

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mentioning

confidence: 59%

Section: In Vitro Assay For the Formation Of Dna Adductsmentioning

confidence: 99%

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confidence: 97%

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Lipid peroxidation and DNA adduct formation in lymphocytes of premenopausal women: Role of estrogen metabolites and fatty acid intake

Sun

Nair

Linseisen

et al. 2012

Intl Journal of Cancer

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“…In addition, the SCE assay does not belong to the genotoxicity tests recommended for regulatory purposes (EFSA Scientific Committee, 2011). Fang et al (2007) administered oleic acid (purity 99%), coconut oil or linoleic acid at a dose of 500 mg/kg bw per day by gavage for 30 days to young adult BD VI rats (4-6 rats/sex per group). The animals were sacrificed and the blood, liver, colon, prostate (males) and breast tissue (females) was collected.…”

Section: Oleic Acidmentioning

confidence: 99%

Re‐evaluation of fatty acids (E 570) as a food additive

Mortensen¹,

Aguilar²,

Crebelli³

et al. 2017

EFS2

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The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re-evaluating the safety of fatty acids (E 570) when used as a food additive. The food additive includes caprylic-(C8), capric-(C10), lauric-(C12), myristic-(C14), palmitic-(C16), stearic-(C18) and oleic acid (C18:1), present alone or in combination. In 1991, the Scientific Committee on Food (SCF) established a group acceptable daily intake (ADI) 'not specified' for the fatty acids (myristic, stearic, palmitic and oleic acid). The fatty acids (E 570) are absorbed in the same way as the free fatty acids from the regular diet. They show low acute toxicity. The available studies on subchronic toxicity were limited but there was no evidence for toxic effects at doses up to 10% in the diet (equivalent to 9,000 mg lauric acid/kg body weight (bw) per day). The Panel considered that the fatty acids (E 570) did not raise a concern for genotoxicity. Data on chronic toxicity, reproductive toxicity and developmental toxicity were too limited to reach a conclusion on these endpoints. The Panel noted that the contribution of fatty acids (E 570) represented on average only 1% of the overall exposure to saturated fatty acids from all dietary sources (food additive and regular diet). Based on the approach described in the conceptual framework for the risk assessment of certain food additives re-evaluated under Commission Regulation (EU) No 257/2010 and taking into account the considerations mentioned above, the Panel concluded that the food additive fatty acids (E 570) was of no safety concern at the reported uses and use levels.

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“…Níveis aumentados dos adutos dAdo e dCyd, provavelmente devido à excessiva geração de produtos da lipoperoxidação, foram detectados em DNA de fígado de ratos da linhagem Long-Evans-Cinnamon conhecidos por acumularem cobre no fígado (Nair et al, 1995). Estes adutos também foram encontrados em níveis aumentados em ratos tratados com ácido linoléico, oléico e óleo de coco (Fang et al, 2007).…”

Section: Eteno Adutosunclassified

Quantificação de danos em DNA induzidos por acetaldeído. Potencial biomarcador de poluição ambiental

García¹

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À FAPESP pelo apoio financeiro e pela bolsa de doutorado. Ao CNPQ, Finep e INCT de processos redox em biomedicina-Redoxoma pelo apoio financeiro À Profa. Dra. Marisa H. G. Medeiros que me aceitou como aluna de iniciação científica quando eu mal sabia o que era DNA e me formou doutora, meu agradecimento e gratidão eternos. Ao Osmar F Gomes, pela amizade, companheirismo, paciência e colaboração de tantos anos. À Profa. Dra. Ana Paula de Melo Loureiro, uma das pessoas mais doces do mundo, que me ensinou desde as primeiras pipetadas até como se portar em um laboratório. À Dra. Sabrina de Almeida Marques, minha também orientadora de Iniciação Cientifica é uma das responsáveis por tudo que me tornei hoje, além de uma excelente amiga a qual sinto muita falta.

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Etheno-DNA adduct formation in rats gavaged with linoleic acid, oleic acid and coconut oil is organ- and gender specific

Cited by 13 publications

References 39 publications

Lipid peroxidation and DNA adduct formation in lymphocytes of premenopausal women: Role of estrogen metabolites and fatty acid intake

Lipid peroxidation and DNA adduct formation in lymphocytes of premenopausal women: Role of estrogen metabolites and fatty acid intake

Re‐evaluation of fatty acids (E 570) as a food additive

Quantificação de danos em DNA induzidos por acetaldeído. Potencial biomarcador de poluição ambiental

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