Bone marrow and liver mutagenesis in lacZ transgenic mice treated with hexavalent chromium.
The mutagenic effects of the hexavalent chromium compound K2CrO4 in lacZ transgenic mice (Muta Mouse) were investigated at two sampling times. K2CrO4 was administered intraperitoneally to five male mice per treatment group at a single dose of 40 mg/kg. The animals were sacrificed on days 1 and 7 after the treatment. Mutant frequencies in the bone marrow and liver were analyzed by the positive selection method using Escherichia coli C (galE-) strain and phenyl beta-D-galactoside. K2CrO4 induced a significant increase in mutant frequency in the bone marrow on day 1, but not on day 7 after the treatment. In the liver, on the other hand, a significant induction in the mutant frequency was seen on day 7, whereas no induction was observed on day 1. The reason for the different responses to the mutagenic activity of K2CrO4 between these organs may be related to their cell turnover rates. The mutations induced by K2CrO4 in the bone marrow may have occurred in more differentiated cells than stem cells, and the rapid proliferative activity may have caused a rapid decrease in mutated cells by day 7. These results suggest that experiments on mutagenesis should be done with more than one sampling point, a short expression time in addition to a longer one, so as to detect mutations induced in organ with high cell proliferation.
Itoh
S
S
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Shimada
H
H
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D002840:Chromates / Q000633:toxicity*; D004247:DNA / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D007763:Lac Operon; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D017680:Potassium Compounds / Q000633:toxicity*; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D002840:Chromates; D009153:Mutagens; D017680:Potassium Compounds; C027373:potassium chromate(VI); D004247:DNA; D001616:beta-Galactosidase