Healy S M, Casarez E A, Ayala-Fierro F, Aposhian H
Department of Pharmacology and Toxicology, University of Arizona, Tucson 85721-0207 USA.
Toxicol Appl Pharmacol. 1998 Jan;148(1):65-70. doi: 10.1006/taap.1997.8306.
With the development of a rapid assay for arsenite methyltransferase (Zakharyan et al., 1995), the specific activity of this critical enzyme for arsenite biotransformation was determined by incubating liver, testis, kidney, or lung cytosol of male B6C3F1 mice with sodium arsenite and S-[methyl-3H]adenosyl-L-methionine and measuring the formation of [methyl-3H]monomethylarsonate. The mean arsenite methyltransferase specific activities (U/mg +/- SEM) measured in these organs were liver, 0.40 +/- 0.06; testis, 1.45 +/- 0.08; kidney, 0.70 +/- 0.06; and lung, 0.22 +/- 0.01. Heretofore, the enzymatic methylation of arsenite has been regarded primarily as a hepatic function. The arsenite methyltransferase specific activity of the testis was 3.6 times greater than that of the liver (p < 0.01) and the specific activity of the kidney was 1.8 times greater than that of the liver (p < 0.05). Additionally, when mice were given arsenate in drinking water for 32 or 91 days at concentrations of 25 or 2500 micrograms As/L, the arsenite methyltransferase activities of liver, testis, kidney, and lung cytosol were not significantly increased in animals receiving either dose of arsenic for either 32 or 91 days compared to controls. No evidence for the induction of arsenite methyltransferase was found under these experimental conditions.
随着亚砷酸盐甲基转移酶快速检测方法的发展(扎卡里扬等人,1995年),通过将雄性B6C3F1小鼠的肝脏、睾丸、肾脏或肺细胞溶胶与亚砷酸钠和S-[甲基-³H]腺苷-L-甲硫氨酸一起孵育,并测量[甲基-³H]一甲基砷酸盐的形成,来确定这种亚砷酸盐生物转化关键酶的比活性。在这些器官中测得的亚砷酸盐甲基转移酶平均比活性(U/mg±标准误)为:肝脏,0.40±0.06;睾丸,1.45±0.08;肾脏,0.70±0.06;肺,0.22±0.01。在此之前,亚砷酸盐的酶促甲基化主要被视为肝脏的功能。睾丸的亚砷酸盐甲基转移酶比活性比肝脏高3.6倍(p<0.01),肾脏的比活性比肝脏高1.8倍(p<0.05)。此外,当给小鼠饮用含25或2500微克砷/升的砷酸盐32天或91天时,与对照组相比,接受任一剂量砷32天或91天的动物肝脏、睾丸、肾脏和肺细胞溶胶的亚砷酸盐甲基转移酶活性均未显著增加。在这些实验条件下未发现亚砷酸盐甲基转移酶被诱导的证据。