Metabolism of polycyclic aromatic hydrocarbons to mutagenic species by rat and porcine ovarian granulosa cells: detection by cocultivation with V79 Chinese hamster cells.
The capacity of ovarian granulosa cells from rat and pig to release reactive metabolites produced from polycyclic aromatic hydrocarbons with the ability to cause mutations in neighbouring cells has been studied. For this purpose we have used cocultivation with V79 Chinese hamster cells as a detection system. The cells were treated with two different polycyclic aromatic hydrocarbons (PAHs), 7,12-dimethylbenz(a)anthracene (DMBA) or (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (BP-7,8-diol). The resulting mutation frequency in the V79 cells after cocultivation, as a function of granulosa cell number, DMBA, or BP-7,8-diol concentration and time, was determined. The progesterone concentration in the medium after cocultivation was also analyzed as a measure of the differentiation of the granulosa cells. These studies demonstrate an increasing frequency of mutations in the V79 cells with an increasing number of granulosa cells. The maximal number of mutations were achieved with a DMBA or BP-7,8-diol concentration of 5 or 2 microM, respectively. The optimal cocultivation time was 24 h. These results clearly show that the granulosa cells can bioactivate PAHs to reactive metabolites with the capacity to migrate into surrounding cells and cause mutations in these cells. Compounds metabolized to mutagenic products by granulosa cells might thus cause mutations in the neighbouring germ cells, with possible consequences for the offspring.
Becedas
L
L
Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.
Romert
L
L
Toft
E
E
Jenssen
D
D
DePierre
J W
JW
Ahlberg
M B
MB
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007700:Kinetics; D009153:Mutagens / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D009154:Mutation; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D011083:Polycyclic Compounds / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine
D004101:Dihydroxydihydrobenzopyrenes; D009153:Mutagens; D011083:Polycyclic Compounds; C017228:benzo(a)pyrene 7,8-dihydrodiol; D011374:Progesterone; D015127:9,10-Dimethyl-1,2-benzanthracene; D007041:Hypoxanthine Phosphoribosyltransferase