Inhibition of meiotic divisions of rat spermatocytes in vitro by polycyclic aromatic hydrocarbons.
The toxic effects of polycyclic aromatic hydrocarbons (PAH) on spermatogenic cells undergoing meiotic division were investigated in vitro. Toxicity was assayed as alterations in cell nucleus morphology and cell survival and by DNA flow cytometry. Benzo[a]pyrene (BP) and 7,12-dimethylbenz[a]anthracene (DMBA) inhibited the progression of spermatocytes through meiotic division and were highly cytotoxic at concentrations higher than 1 microM. These results were obtained upon addition of a drug-metabolizing system, indicating that the seminiferous tubules lack the enzymes required for the initiation of PAH metabolism. The spindle poisons, e.g., vincristine and Colcemid, a group of direct-acting agents, affected spermatogenesis during meiotic division in a manner similar to that observed with PAH. In contrast, adriamycin did not inhibit meiotic division, although it did induce the formation of meiotic micronuclei as a result of chromosome breakage. It is concluded that low concentrations, i.e., 0.1 microM of PAH, strongly inhibit meiotic division, presumably after metabolic activation to reactive molecules functionally resembling direct-acting alkylating agents. High concentrations of PAH are cytotoxic.
Georgellis
A
A
Wallenberg Laboratory, Department of Biochemistry, University of Stockholm, Sweden.
Toppari
J
J
Veromaa
T
T
Rydström
J
J
Parvinen
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D001711:Biotransformation; D004247:DNA / Q000032:analysis; D003703:Demecolcine / Q000633:toxicity; D005434:Flow Cytometry; D008297:Male; D008540:Meiosis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013090:Spermatocytes / Q000166:cytology / Q000187:drug effects*; D014750:Vincristine / Q000633:toxicity
D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D014750:Vincristine; D004247:DNA; D003703:Demecolcine