Evidence for mitochondrial metabolism of 7,12-dimethylbenz(a)anthracene in porcine ovaries: comparison with microsomal metabolism

• Published in: Toxicology (Amsterdam) Vol. 122; no. 1; pp. 11 - 21
• Main Authors: Eliasson, Maria, Brock, Stephan, Bengtsson Ahlberg, Margot
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 26.09.1997; Amsterdam Elsevier Science
• Subjects: 7,12-dimethylbenz(a)anthracene; 9,10-Dimethyl-1,2-benzanthracene - pharmacokinetics; Animals; Biological and medical sciences; Biotransformation; Chemical and industrial products toxicology. Toxic occupational diseases; Corpus Luteum - enzymology; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450; Female; Medical sciences; Microsomes - enzymology; Microsomes - metabolism; Mitochondria; Mitochondria - enzymology; Mitochondria - metabolism; Monoamine Oxidase - metabolism; NADH, NADPH Oxidoreductases - metabolism; Ovarian Follicle - enzymology; Ovary; Ovary - enzymology; Ovary - metabolism; Ovary - ultrastructure; Porcine; Stilbenes - pharmacokinetics; Swine; Toxicology; Various organic compounds; PGS, prostaglandin synthetase; Porcine; mEH, microsomal epoxide hydrolase; Cytochrome P450; PAH, polycyclic aromatic hydrocarbon; BCA, bicinchoninic acid; DMBA, 7,12-Dimethylbenz(a)anthracene; Ovary; Mitochondria; TCDD, 2,3,7,8-tetrachlorodibenzo- p-dioxin; MAO, monoamine oxidase; 7,12-dimethylbenz(a)anthracene; P450, cytochrome P450; CYP, cytochrome P450 as recommended by the Nomenclature Committee ( Nelson et al., 1993); Polycyclic aromatic compound; Microsome; Metabolism; Pig; Vertebrata; Mammalia; Animal; Corpus luteum; Artiodactyla; Ungulata
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(97)00074-7

7,12-dimethylbenz(a)anthracene (DMBA) causes necrosis in endocrine organs. DMBA metabolism in follicles and corpora lutea from porcine ovaries was demonstrated not only in the microsomal but also in the mitochondrial fraction, in contrast to what has been found in the rat ovary. Maximal activities were present in these fractions of the corpus luteum, with specific activities of 5.9 and 2.2 pmol/min×mg protein, respectively. DMBA metabolism in mitoplasts, i.e. mitochondrial inner membranes, proved to be more than 10-fold higher than the corresponding activity in the mitochondrial fraction. The purities of the subcellular fractions were assessed by measurements of marker enzymes. 17–42% of the mitochondrial DMBA metabolism was concluded to be due to microsomal contamination. In the mitoplast fraction such contamination was only 0.18–2.8%. Ellipticine and α-naphthoflavone reduced the metabolism of DMBA in the luteal microsomal fraction by 95 and 77%, respectively. In mitochondria the inhibition by these agents was 63 and 30%, respectively. Indomethacine and estradiol decreased microsomal DMBA metabolism by 53 and 52%, respectively. In mitochondria the inhibition was 52 and 23%, respectively. None of these inhibitors affected the DMBA metabolism by the mitoplast fraction.