Olive P L, Durand R E
Br J Cancer Suppl. 1978 Jun;3:124-8.
Hypoxic cells can metabolize nitroheterocyclic compounds to produce toxic intermediates capable of affecting the survival of neighbouring oxygenated cells. Mutagenesis experiments with E. coli WP-2 343 (deficient in nitroreductase) indicated that reduction of nitroheterocyclics outside bacteria causes killing and mutations within bacteria, presumably due to the transfer of the "active" specie (s). Using animal tissue slices to reduce nitrofurans, cultured L-929 cells incubated under aerobic conditions were far more sensitive to the toxic and DNA damaging effects of these drugs. Transfer of the active species also occurs in a tissue-like environment in multicell spheroids where the presence of a hypoxic central core served to convert the nitroheterocyclics to intermediates which also damaged the neighbouring oxygenated cells.
缺氧细胞能够代谢硝基杂环化合物，产生能够影响邻近含氧细胞存活的有毒中间体。对大肠杆菌WP-2 343（缺乏硝基还原酶）进行的诱变实验表明，细菌外硝基杂环化合物的还原会导致细菌内的杀伤和突变，这可能是由于“活性”物质的转移所致。使用动物组织切片来还原硝基呋喃，在有氧条件下培养的L-929细胞对这些药物的毒性和DNA损伤作用更为敏感。活性物质的转移也发生在多细胞球体的类似组织的环境中，其中缺氧的中央核心的存在有助于将硝基杂环化合物转化为中间体，这些中间体也会损害邻近的含氧细胞。
