The nervous system specificity of the carcinogenic effect of N-ethyl-N-nitrosourea Present evidence suggests that the probability of neoplastic transformation is not a simple function of the degree of cellular interaction with an oncogenic agent, but is also strongly dependent on the proliferative and functional state of the target cell (6, 1). In the search for cellular determinants of malignant transformation the tissue specificity of carcinogens may be a factor of considerable heuristic value, provided it is not primarily due to activation of the compounds by enzymes particularly active in the tissues in question.The carcinogenic (8) and mutagenic (9) acylalkylnitrosamide N-ethyl-N-nitrosourea (EtNU) yields an electrophilic ethyl cation via nonenzymatic, heterolytic decomposition, occurring with a half-life of about 8 min under physiological conditions (7). A single pulse of EtNU, applied to fetal or newborn rats up to an age of 10-20 days, specifically results in a high incidence of malignant neuroectodermal tumors associated with the central and peripheral nervous system (refs.
NOTIZENthis effect. These data and the findings of the reversibility of the pH-effect and the non-reversibility of the uptake make the following hypothesis likely; the pHeffect, illustrated in Fig. 1
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