Long-Evans A and C Rat Strains Susceptible to Clastogenic Effects of Chemicals in the Bone Marrow Cells

The Clastogenic responses to direct- and indirect-acting carcinogens in bone marrow cells of LEA, LEC, Wistar and SD rats were compared. The frequency of chromosome aberrations (CA) induced by n -butyl-N-nitrosourea or methylmethanesulfonate (MMS), which does not need metabolic activation, was significantly higher in both LEA and LEC rats than in Wistar or SD rats. When bone marrow cells of each rat strain were exposed to MMS in vitro , they also showed the same tendency in CA frequency. Therefore, the high sensitivity of both LEA and LEC rats to the Clastogenic effects of direct-acting carcinogens seems to result from the sensitivity of the bone marrow cells themselves. On the other hand, the CA frequency induced by 7,12-dimethylbenz[a]anthracene (DMBA) or aflatoxin bi (AFB₁), which requires metabolic activation, was lower in LEC rats than in the other 3 strains. The CA frequency induced by DMBA or AFB₁ in LEC rats fed Cu-free diet since birth (Cu-free LEC rats) was higher than that in LEC rats given normal diet and lower than that in LEA rats, although the difference was statistically significant only between Cu-free LEC rats and LEC rats treated with DMBA. The copper concentrations in the livers of LEA, Cu-free LEC and LEC male rats aged 4 weeks were 5.0 ±0.4, 33 ±7.7 and 106±3.4 μg/g wet weight, respectively. These results suggest that the lower sensitivity of LEC rats to the Clastogenic effects of indirect-acting carcinogens may be due to the effect of the large amount of copper accumulated in LEC rat liver.