Ruchirawat M, Shank R C
J Toxicol Environ Health. 1978 Jan;4(1):161-72. doi: 10.1080/15287397809529653.
The relationship between oxidative metabolism and acute toxicity of dimethylnitrosamine (DMN) was examined in neonatal and adult rats to take advantage of developmental changes in activity of the metabolizing enzymes. The objective was to determine the extent to which CO2 production from DMN is correlated with toxicity. Neonatal rat liver and kidney demonstrated the ability to metabolize DMN. This ability progressed to a maximum activity in liver between the 5th and 21st d of age and in kidney between the 15th and 21st d of age. After weaning, the activity of DMN oxidation decreased with age in both tissues. Evidence is also presented to suggest that more than one enzyme may be responsible for the oxidation of DMN to CO2 and that the predominance of individual enzymes varies as the neonate develops. Estimates of LD50 values, used to quantitate the acute toxicity of DMN at various ages, suggest that the rat is most sensitive to DMN toxicity at 5 d of age; however, conversion of DMN to CO2, both in vitro and in vivo, was not well correlated with acute toxicity.
为利用代谢酶活性的发育变化，研究了新生大鼠和成年大鼠中氧化代谢与二甲基亚硝胺（DMN）急性毒性之间的关系。目的是确定DMN产生的二氧化碳与毒性之间的相关程度。新生大鼠的肝脏和肾脏表现出代谢DMN的能力。这种能力在出生后第5至21天在肝脏中发展到最大活性，在出生后第15至21天在肾脏中发展到最大活性。断奶后，两种组织中DMN氧化活性均随年龄下降。还有证据表明，可能不止一种酶负责将DMN氧化为二氧化碳，并且随着新生儿的发育，各个酶的优势会发生变化。用于定量不同年龄DMN急性毒性的半数致死剂量（LD50）值估计表明，大鼠在5日龄时对DMN毒性最敏感；然而，DMN在体外和体内转化为二氧化碳的过程与急性毒性的相关性并不好。
