Kiyohara C, Mohri N, Hirohata T, Haraguchi K, Masuda Y, Nagayama J
Department of Public Health, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Toxicol Lett. 1990 Jun;52(1):73-80. doi: 10.1016/0378-4274(90)90167-k.
The effects of in vivo administration of polycyclic aromatic hydrocarbons on the levels of aryl hydrocarbon hydroxylase (AHH) activity in aromatic hydrocarbon (Ah) responsive and non-responsive strains of mice were studied using the hepatic microsomal fraction. Injection of 3-methylcholanthrene (MC; 42 mg/kg body wt.) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 120 micrograms/kg body wt.) into both strains produced marked enhancement of AHH activity except for MC treatment of Ah non-responsive strains. Addition of 7,8-benzoflavone (BNF) to the microsomal AHH assay mixture prepared from mice previously injected with vehicle (olive oil) alone caused an increase in activity when the mice were responsive, while BNF lowered the activity in non-responsive strains. With regard to MC-injected mice, BNF and 3-methyl-sulphonyl-4,5,3',4'-tetrachlorobiphenyl (3-MSF-TCB) decreased microsomal AHH activity in Ah-responsive mice, whereas these drugs enhanced the activity in Ah-non-responsive strains. 3-MSF-TCB also had inhibitory potency on AHH activity, but the mechanism of inhibition seems to be somewhat different from that of BNF. It may also suggest that cytochrome P-450 isozymes inhibited by BNF are different from those inhibited by 3-MSF-TCB.
使用肝微粒体部分,研究了体内给予多环芳烃对芳烃(Ah)反应性和非反应性小鼠品系中芳烃羟化酶(AHH)活性水平的影响。向两个品系的小鼠注射3-甲基胆蒽(MC;42毫克/千克体重)或2,3,7,8-四氯二苯并对二恶英(TCDD;120微克/千克体重)后,除了对Ah非反应性品系进行MC处理外,均使AHH活性显著增强。向仅预先注射了赋形剂(橄榄油)的小鼠制备的微粒体AHH测定混合物中添加7,8-苯并黄酮(BNF),当小鼠有反应时会导致活性增加,而BNF会降低非反应性品系中的活性。对于注射了MC的小鼠,BNF和3-甲基磺酰基-4,5,3',4'-四氯联苯(3-MSF-TCB)会降低Ah反应性小鼠的微粒体AHH活性,而这些药物会增强Ah非反应性品系中的活性。3-MSF-TCB对AHH活性也有抑制作用,但其抑制机制似乎与BNF有所不同。这也可能表明,被BNF抑制的细胞色素P-450同工酶与被3-MSF-TCB抑制的不同。