CADMIUM DISPOSITION AND METALLOTHIONEIN INDUCTION IN MICE - STRAIN-DEPENDENT, SEX-DEPENDENT, AGE-DEPENDENT AND DOSE-DEPENDENT DIFFERENCES

The strain- and sex-related differences in tissue cadmium (Cd) and met allothionein (MT) levels were examined in young adult (4-6 months old) C3H/HeJ, DBA/2J, 129/J, CD-1 and A/J mice, 24 h after a subcutaneous (s.c.) injection of 5-30 mumol CdCl2/kg. In many cases the tissue Cd c oncentrations were inversely related to the tissue weights. Also, the strain and sex differences were more obvious at 20-30-mumol dose level s. At such doses the hepatosensitive C3H males had as much as 30% high er hepatic Cd concentrations as the resistant DBA males, but similar c oncentrations to the resistant A/J and CD-1 males. This observation su ggests that tissue Cd level is not the only determinant of strain diff erences in hepatotoxicity in males. Among the females, the A/J had 30- 47% higher hepatic Cd concentration than the other strains. Livers of male C3H, CD-1 and 129/J mice had 17-57% higher Cd concentrations than those of the females; the greatest difference was in the C3H strain i n which only the males exhibited hepatotoxicity at the 30 mumol dose. In all animals the hepatic MT concentration increased with the increas ing Cd concentration. However, the 129/J males and all the females rea ched a plateau in MT concentration at Cd concentrations of 20-30 mug/g liver. Even at the highest Cd concentration, the C3H males had MT con centrations similar to some of the hepatoresistant males, suggesting t hat their sensitivity to Cd was not due to compromised MT levels. The renal Cd concentration was similar in males of most strains but not in females. For example, at the 30-mumol dose 129/J females had a Cd con centration which was 70% higher than in the DBA females. Also, at this dose level the A/J, C3H and 129/J females had 30-50% more Cd than the males. The DBA and C3H males had approximately twice the MT concentra tion of the A/J and 129/J males at 10 mug Cd/g kidney. At similar Cd c oncentration, the DBA females also had 1.6-2.0 times the MT concentrat ion of the other females. The renal MT levels in females were 1.4-2.9 times higher than in males. Strains susceptible to the testicular toxi city of Cd had up to three times greater testicular Cd accumulation th an the resistant strains. However, there was no increase in testicular MT in any strain. The effect of age on Cd and MT levels was studied i n 19-month-old A/J and DBA mice at the 25-mumol dose. The aged mice ha d 15-42% higher hepatic Cd concentration than the younger animals; how ever, their MT levels were the same. The renal Cd, but not MT, concent ration in the older animals was 25-33% lower than in young animals. De spite the larger body weights the Cd-injected aged males had 22-29% sm aller testes, but about the same amount of Cd, as the young males, sug gesting that the older DBA males may exhibit testicular toxicity at a lower dose of Cd than the young animals. Thus, it is concluded that no t only the dose but also the strain, sex and age of the animal are imp ortant factors in determining the disposition of Cd in mice. The diffe rences in the tissue Cd accumulation may relate to variations in hormo nal and other intrinsic factors affecting the cellular uptake and subc ellular distribution of Cd and biosynthesis and degradation of MT.