BONE-MARROW AND LIVER MUTAGENESIS IN LACZ TRANSGENIC MICE TREATED WITH HEXAVALENT CHROMIUM

The mutagenic effects of the hexavalent chromium compound K2CrO4 in la cZ transgenic mice (Muta(TM) 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 sacrif iced on days 1 and 7 after the treatment. Mutant frequencies in the bo ne marrow and liver were analyzed by the positive selection method usi ng 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, o n 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 betwee n these organs may be related to their cell turnover rates. The mutati ons induced by K2CrO4 in the bone marrow may have occurred in more dif ferentiated cells than stem cells, and the rapid proliferative activit y may have caused a rapid decrease in mutated cells by day 7, These re sults suggest that experiments on mutagenesis should be done with more than one sampling point, a short expression time in addition to a lon ger one, so as to detect mutations induced in organ with high cell pro liferation. (C) 1998 Elsevier Science B.V.