Correlation between DNA or protein adducts and benzo[a]pyrene diol epoxide I-triglyceride adduct detected in vitro and in vivo

In this study, we demonstrated the in vitro and in vive formation of carcinogen-lipid adduct and its correlation with DNA or protein adducts, The lipids from serum or hepatocyte membranes of Sprague-Dawley rats, human serum and standard major lipids were in vitro reacted with benzo[a]pyrene (B[a]P) and B[a]P metabolites. 7,8-Dithydroxy-9,10-epoxy-7,8,9,10-tetrahydr benzo[a]pyrene (BPDE-I), an ultimate carcinogenic form of B[a]P, was covalently bound to triglyceride (TG), BPDE-I-TG adducts isolated by thin-layer chromatography (TLC) were further detected by high-performance liquid chromatography, TGs, including triolein, tripalmitin and tristearin, showed positive reactions with BPDE-I, However, cholesterol, phospholipids (phosphatidylcholine, phosphatidyl-ethanolamine, phosphatidyl-inositol and sphingomyelin) and nonesterified fatty acids (palmitic acid, oleic acid, linoleic acid and stearic acid) did not react with BPDE-I, In addition, other B[a]P metabolites (B[a]P-phenols and -diols) did not react with TG, TG appeared to be the most reactive lipid yet studied with respect to its ability to form an adduct with BPDE-I, There was a clear-cut dose-related formation of [1,3-B-3]BPDE-I-lipid adducts in vitro between TG and [1,3-H-3]BPDE-I, In an animal study, BPDE-I-TG was also formed in the serum of rats orally treated with B[a]P (25 mg/rat), Also, obvious correlations between [H-3]B[a]P related-biomolecule adducts (DNA or protein) or lipid damage and the BPDE-I-TG adducts were obtained in various tissues of mice i,p, treated with [H-3]B[a]P. These data suggest that TG can form an adduct with BPDE-I, as do other macromolecules (DNA, RNA and protein). Therefore, a carcinogen-lipid adduct would be a useful biomarker for chemical carcinogenesis research and cancer risk assessment.