Etheno-DNA adduct formation in rats gavaged with linoleic acid, oleic acid and coconut oil is organ- and gender specific.
Intake of linoleic acid (LA) increased etheno-DNA adducts induced by lipid peroxidation (LPO) in white blood cells (WBC) of female but not of male volunteers [J. Nair, C.E. Vaca, I. Velic, M. Mutanen, L.M. Valsta, H. Bartsch, High dietary omega-6 polyunsaturated fatty acids drastically increase the formation of etheno-DNA adducts in white blood cells of female subjects, Cancer Epidemiol. Biomarkers Prev. 6 (1997) 597-601]. Etheno-adducts were measured in rats gavaged with LA, oleic acid (OA) and saturated fatty acid rich coconut oil for 30 days. DNA from organs and total WBC was analyzed for 1, N(6)-ethenodeoxyadenosine (varepsilondA) and 3, N(4)-ethenodeoxycytidine (varepsilondC) by immunoaffinity/(32)P-postlabeling. Colon was the most affected target with LA-treatment, where etheno-adducts were significantly elevated in both sexes. In WBC both adducts were elevated only in LA-treated females. Unexpectedly, OA treatment enhanced etheno-adduct levels in prostate 3-9 fold. Our results in rodents confirm the gender-specific increase of etheno-adducts in WBC-DNA, likely due to LPO induced by redox-cycling of 4-hydroxyestradiol. Colon was a target for LPO-derived DNA-adducts in both LA-treated male and female rats, supporting their role in omega-6 PUFA induced colon carcinogenesis.
Fang
Qingming
Q
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280 69120 Heidelberg, Germany.
Nair
Jagadeesan
J
Sun
Xin
X
Hadjiolov
Dimiter
D
Bartsch
Helmut
H
D000818:Animals; D002417:Cattle; D000074263:Coconut Oil; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000209:etiology; D018736:DNA Adducts / Q000032:analysis / Q000096:biosynthesis*; D003839:Deoxyadenosines / Q000032:analysis; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D019787:Linoleic Acid / Q000008:administration & dosage / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D019301:Oleic Acid / Q000008:administration & dosage / Q000633:toxicity*; D009928:Organ Specificity; D010938:Plant Oils / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D012727:Sex Characteristics
D018736:DNA Adducts; D003839:Deoxyadenosines; D010938:Plant Oils; D003841:Deoxycytidine; D019301:Oleic Acid; C032221:1,N(6)-ethenodeoxyadenosine; C032222:3,N(4)-ethenodeoxycytidine; D019787:Linoleic Acid; D000074263:Coconut Oil