Inhibition of stage-specific DNA synthesis in rat spermatogenic cells by polycyclic aromatic hydrocarbons.
Changes in the rate of DNA synthesis in spermatogenic cells after treatment of segments of rat seminiferous tubule at defined stages of epithelial cycle with benzo[a]pyrene (BP) or 7,12-methylbenz[a]anthracene (DMBA) were studied. The incorporation of labeled thymidine into DNA was used as a measure of the rate of DNA synthesis. Very little or no inhibition of DNA synthesis at stages V and VIII of the cycle was observed at BP and DMBA concentrations lower than 100 microM. In contrast, in the presence of added mitochondria and/or microsomes from whole rat testis, 20 microM BP or DMBA inhibited DNA synthesis 5% and 80%, respectively. This inhibition of DNA synthesis was prevented by inhibitors of the cytochrome P-450 system and by free radical scavengers. These results suggest that polycyclic aromatic hydrocarbons (PAH) require metabolic activation in order to inhibit DNA replication in seminiferous tubules. The first step of this biotransformation is cytochrome P-450-dependent and occurs in Leydig cells. However, the metabolites produced in this step may be further metabolized to reactive metabolites by peroxidative pathways in the seminiferous tubules; these latter products may affect DNA replication.
Georgellis
A
A
Department of Biochemistry, Arrhenius Laboratory, University of Stockholm, Sweden.
Parvinen
M
M
Rydström
J
J
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D004247:DNA / Q000096:biosynthesis*; D005609:Free Radicals; D008297:Male; D008861:Microsomes / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012671:Seminiferous Tubules / Q000166:cytology / Q000187:drug effects; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism*
D065607:Cytochrome P-450 Enzyme Inhibitors; D005609:Free Radicals; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA