POLYCYCLIC AROMATIC-HYDROCARBONS CAUSE HEPATIC PORPHYRIA IN IRON-LOADED C57BL-10 MICE - COMPARISON OF UROPORPHYRINOGEN DECARBOXYLASE INHIBITION WITH INDUCTION OF ALKOXYPHENOXAZONE DEALKYLATIONS
POLYCYCLIC AROMATIC-HYDROCARBONS CAUSE HEPATIC PORPHYRIA IN IRON-LOADED C57BL-10 MICE - COMPARISON OF UROPORPHYRINOGEN DECARBOXYLASE INHIBITION WITH INDUCTION OF ALKOXYPHENOXAZONE DEALKYLATIONS
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DOI：
10.1016/0006-291x(87)90683-8
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发表时间：
1987-07-15
影响因子：
3.1
通讯作者：
SMITH, AG
中科院分区：
文献类型：
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作者：
FRANCIS, JE;SMITH, AG
多剂量β-萘黄酮铁负荷的C57BL/10ScSn小鼠连续6周，可引起肝脏尿卟啉原脱羧酶的抑制和一种与以往报道的多卤代芳香族化合物难以区分的卟啉症。β-萘黄酮和细胞色素P1-450介导的乙氧基苯并恶宗脱乙基酶的其他多环芳烃诱导剂、苯并[a]芘、苯并[a]菲、联苯并[啊]菲、3-甲基胆菲和α-萘黄酮在进食时也会产生卟啉。异黄樟素是无效的，但苯巴比妥对脱羧酶有轻微但显著的抑制作用。结果表明，多环芳烃的毒性作用可能不涉及反应性代谢产物。
Multiple doses of .beta.-naphthoflavone to iron-loaded C57BL/10ScSn mice for 6 weeks caused inhibition of hepatic uroporphyrinogen decarboxylase and a porphyria indistinguishable from that previously only reported for polyhalogenated aromatic chemicals. .beta.-Naphthoflavone and other polycyclic aromatic hydrocarbon inducers of cytochrome P1-450-mediated ethoxyphenoxazone deethylation (ethoxyresorufin deethylase), benzo[a]pyrene, benz[a]anthracene, dibenz[ah]anthracene, 3-methylcholanthrene and .alpha.-naphthoflavone, also gave porphyria when fed. Isosafrole was inactive but by both methods phenobarbital produced a small but singificnat inhibition of the decarboxylase. The results demonstrate a toxic action of polycyclic aromatic hydrocarbons which probably does not involve reactive metabolites.