In vivo studies on chemically induced aneuploidy in mouse somatic and germinal cells.
Within the context of a coordinated program to study aneuploidy induction sponsored by the European Community, nine chemicals were tested in mouse bone marrow and spermatocytes after intraperitoneal injection. In somatic cells, cell progression delay, hyperploidy, polyploidy induction and induction of micronucleated polychromatic erythrocyte (MnPCE) were studied. In germ cells hyperploidy induction was evaluated. The chemicals selected were: colchicine (COL), econazole (EZ), hydroquinone (HQ), thiabendazole (TB), diazepam (DZ), chloral hydrate (CH), cadmium chloride (CD), pyrimethamine (PY) and thimerosal (TM). Using literature data on c-mitotic effects in bone marrow as a reference, the same doses were tested in somatic and germ cells in order to compare the effects induced. Bone marrow cells were sampled 18 or 24 h after treatment. Germ cells were sampled 6, 8 or 18 h after treatment. Effects of COL and HQ in bone marrow have been reported elsewhere. Somatic effects were induced by CH (hyperploidy and cell cycle lengthening), TB (MnPCEs and cell cycle lengthening) and by PY (MnPCEs). EZ, DZ, CD and TM did not induce any kind of somatic effects. An increase in the incidence of hyperploid spermatocytes was induced by COL, at three dose levels, and by one dose of HQ and TB. All the other chemicals did not induce germinal aneuploidy at any dose or time tested. The hyperploidy control frequency ranged between 0.4 and 1.0% in somatic cells and from 0.3 to 0.9% in germ cells. In both somatic and germ cells, the maximum yield of induced hyperploidy did not exceed 3.5%. The time period of target cell sensitivity is probably restricted and this, associated with the heterogeneity and the asynchrony of cellular maturation processes, may account for our data. Under these circumstances, the negative data should be interpreted with some caution, particularly in germ cells, where additional indicators of chemical-cell interaction and cell cycle effects were not provided by standardized approaches. The possibility of increasing the size of analyzed cell samples could be considered in the light of automatic scoring procedures.
Leopardi
P
P
Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanità, Rome, Italy.
Zijno
A
A
Bassani
B
B
Pacchierotti
F
F
D000782:Aneuploidy; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D002104:Cadmium / Q000633:toxicity; D019256:Cadmium Chloride; D002697:Chloral Hydrate / Q000633:toxicity; D002712:Chlorides / Q000633:toxicity; D003078:Colchicine / Q000633:toxicity; D003975:Diazepam / Q000633:toxicity; D004464:Econazole / Q000633:toxicity; D006873:Hydroquinones / Q000633:toxicity; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015162:Micronucleus Tests / Q000379:methods; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011003:Ploidies; D011739:Pyrimethamine / Q000633:toxicity; D013090:Spermatocytes / Q000166:cytology / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013827:Thiabendazole / Q000633:toxicity; D013849:Thimerosal / Q000633:toxicity
D002712:Chlorides; D006873:Hydroquinones; D009153:Mutagens; D002104:Cadmium; D013849:Thimerosal; D002697:Chloral Hydrate; D004464:Econazole; D019256:Cadmium Chloride; D013827:Thiabendazole; D003975:Diazepam; D003078:Colchicine; C031927:hydroquinone; D011739:Pyrimethamine