Ashby J, Lefevre P A
Carcinogenesis. 1982;3(11):1273-6. doi: 10.1093/carcin/3.11.1273.
The rate of hydrolysis to formaldehyde of methylenedimorpholine (MDM), hexamethylenetetramine (HMT) and dinitrosopentamethylenetetramine (DNPT) have been compared with the enzyme-mediated formation of formaldehyde from hexamethylphosphoramide (HMPA). The bio-distribution of [14C]HMPA following nasal instillation in rats has also been studied and compared with that of [14C]methyl methanesulphonate (MMS). These data are used to relate the several carcinogenic/genotoxic properties of the chemicals named above. It is concluded from these data and related considerations that three classes of formaldehyde-generators should be recognized (a) labile agents such as MDM (and formaldehyde) which are likely to be locally active as carcinogens, (b) lipophilic and relatively stable agents such as HMPA which may be both locally active (if bio-accumulated) and systemically active as carcinogens, and (c) agents such as HMT and DNPT, of intermediate stability, which are unlikely to be systemically active and to be of low or zero activity locally.
已将亚甲基二吗啉（MDM）、六亚甲基四胺（HMT）和二亚硝基五亚甲基四胺（DNPT）水解为甲醛的速率与酶介导的六甲基磷酰胺（HMPA）生成甲醛的速率进行了比较。还研究了大鼠经鼻滴注[14C]HMPA后的生物分布，并与[14C]甲磺酸甲酯（MMS）的生物分布进行了比较。这些数据用于关联上述化学品的几种致癌/遗传毒性特性。从这些数据及相关考虑得出结论，应识别出三类甲醛生成剂：（a）不稳定试剂，如MDM（和甲醛），它们可能作为致癌物在局部具有活性；（b）亲脂性且相对稳定的试剂，如HMPA，其可能在局部（如果生物蓄积）具有活性且作为致癌物具有全身活性；（c）稳定性中等的试剂，如HMT和DNPT，它们不太可能具有全身活性且在局部具有低活性或无活性。
