Organ variation in the mutagenicity of ethylnitrosourea in Muta mouse: results of the collaborative study on the transgenic mutation assay by JEMS/MMS. The Collaborative Study Group for the Transgenic Mouse Mutation Assay Mammalian Mutagenesis Study Group of the Environmental Mutagen Society of Japan.

Abstract

A collaborative study of the transgenic mouse mutation assay was performed by a subgroup of the Mammalian Mutagenesis Study Group (MMS), which is a suborganization of the Environmental Mutagen Society of Japan (JEMS). Twenty-six laboratories participated in this collaboration, and ethylnitrosourea (ENU) mutagenesis was studied in eight organs of lacZ transgenic mice (Muta Mouse)-liver, spleen, bone marrow, brain, lung, kidney, urinary bladder, and heart. Mice were treated by a single intraperitoneal (ip) injection of 150 mg/kg ENU, and the lacZ mutant frequency (MF) was analyzed by positive selection after 3- and 14-day expression times. The MF in the control group was similar for all organs, approximately 40-60 x 10(-6). ENU increased MF in all organs except the brain with the highest values (more than 10 times the control value) observed in bone marrow on days 3 and 14, and in spleen on day 14. The MF in urinary bladder increased over 400 x 10(-6) and MFs in liver and lung were more than 150 x 10(-6) on day 14, although no increases were apparent in these organs on day 3. Approximately a doubling of control values was observed in kidney and heart but these were less than 100 x 10(-6). These results demonstrated that ENU induces organ specific mutagenesis with specific expression periods.