Hepatic isometallothioneins in mice: induction in adults and postnatal ontogeny.
The purpose of this study was to quantitate hepatic metallothionein-I (MT-I) and metallothionein-II (MT-II) in adult mice pretreated with various dosages of selected inorganic and organic compounds and in nonchemically treated neonatal mice. Male CF-1 mice received Zn (0.38-6.0 mmol/kg, sc), Cd (5-80 mumol/kg, sc), dexamethasone (10-1000 mumol/kg, sc), or ethanol (60-180 mmol/kg, po). Liver cytosol was prepared 24 hr after the administration of each compound. In another experiment, liver cytosols were prepared from male and female neonates 1 to 35 days after parturition. MT-I and MT-II in liver cytosols were isolated by high-performance anion-exchange chromatography and quantitated by atomic absorption spectrometry. Hepatic MT-I and MT-II concentrations in adult controls were 5.1 +/- 1.3 and 3.7 +/- 1.0 micrograms/g liver, respectively. All compounds increased hepatic MT levels in a dose-dependent manner over a narrow range of dosages. The lowest dosages of Zn, Cd, dexamethasone, and ethanol that produced a significant increase in total MT content (MT-I plus MT-II) were 0.38, 0.005, 0.3, and 90 mmol/kg, respectively. Maximal induction of total MT following the highest dosages of Zn, Cd, ethanol, and dexamethasone was 58, 34, 24, and 13 times the control value (8.8 +/- 2.4 micrograms total MT/g liver), respectively. The relationship between dose and hepatic MT content was linear following ethanol administration and log-linear following Zn, Cd, and dexamethasone administration. The ratio of MT-I/MT-II was approximately 2.4 following all dosages of metals. Following low and high dosages of organic compounds, the ratio of MT-I/MT-II was approximately 1.0 and 1.5, respectively. Total MT concentration in livers of 1- to 14-day-old mice was approximately 40 times that observed in adult liver (5.5 +/- 1.6 micrograms total MT/g liver) and returned toward adult levels 21 days after parturition. The ratio of MT-I/MT-II was approximately 1.8 during Postpartum Days 1 through 14 and thereafter decreased to approximately 1.0. These results indicate that MT-I is more abundant than MT-II in mouse liver following chemical exposure and during neonatal development.
Kershaw
W C
WC
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Lehman-McKeeman
L D
LD
Klaassen
C D
CD
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D001711:Biotransformation / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D013054:Spectrophotometry, Atomic; D015032:Zinc / Q000494:pharmacology*
D002104:Cadmium; D000431:Ethanol; D003907:Dexamethasone; D008668:Metallothionein; D015032:Zinc