Barale R, Zucconi D, Romano M, Loprieno N
Mutat Res. 1983 Feb;113(1):21-32. doi: 10.1016/0165-1161(83)90238-8.
The intragastric host-mediated assay (h.m.a.) was devised and carried out with a view to assessing the formation of direct mutagens in the gastrointestinal tract of mammals. The h.m.a. consists in the injection of nitrosable compounds, NaNO2 and cells of the yeast S. pombe, by gavage into the animals' stomachs and in the recovery of the target cells from the faeces for mutation-induction analysis. Methylurea was chosen as a model nitrosable compound, and the effects of nitrosation modulators such as ascorbic acid and thiocyanate were studied. Cimetidine, a drug nitrosable in vitro, was tested with the system. Positive results were obtained only at very large doses and in artificially produced low pH. The new host-mediated assay seems to be efficient in revealing the formation, in vivo, of direct, short-living mutagens.
为评估哺乳动物胃肠道中直接诱变剂的形成,设计并开展了胃内宿主介导试验(h.m.a.)。该试验包括通过灌胃将可亚硝化的化合物、亚硝酸钠和粟酒裂殖酵母细胞注入动物胃内,并从粪便中回收靶细胞进行诱变分析。选择甲基脲作为可亚硝化化合物的模型,并研究了抗坏血酸和硫氰酸盐等亚硝化调节剂的作用。用该系统测试了在体外可亚硝化的药物西咪替丁。仅在非常大的剂量和人工产生的低pH条件下获得了阳性结果。新的宿主介导试验似乎能有效地揭示体内直接的、寿命短的诱变剂的形成。