Kouri R E, Connolly G M, Nebert D W, Lubet R A
Int J Cancer. 1983 Dec 15;32(6):765-8. doi: 10.1002/ijc.2910320618.
The relationship between the Ah locus and the induction of subcutaneous fibrosarcomas by dibenz[a,h]anthracene and dibenz[a,c]anthracene was investigated in C57BL/6J (Ahb/Ahb), (C57BL/6J)(DBA/2J)F1 (Ahb/Ahd) and (Ahd/Ahd) mice. Ahb/Ahb and Ahb/Ahd mice have the high-affinity Ah receptor and therefore the polycyclic hydrocarbon induction of aryl hydrocarbon hydroxylase activity (cytochrome P1-450) proceeds with ease; Ahd/Ahd mice have the poor-affinity Ah receptor and this induction process proceeds more poorly, by a factor of at least 10-fold. Dibenz[a,c]anthracene proved to be a relatively weak carcinogen, producing less than 3% tumor incidence at doses up to 300 micrograms per mouse. In contrast, dibenz[a,h]anthracene caused an almost 50% tumor incidence in Ahb/Ahb and Ahb/Ahd mice, while causing approximately 2% tumor incidence in Ahd/Ahd mice. Both isomers bind avidly to the cytosolic Ah receptor, and both chemicals induce aryl hydrocarbon hydroxylase activity in Ahb/Ahb and Ahd/Ahd animals. Among progeny of the (C57BL/6J) (DBA/2J) F1 X DBA/2J backcross, 63 of 100 Ahb/Ahd mice and none of 75 Ahd/Ahd mice developed tumors. These data demonstrate a strict correlation between susceptibility to dibenz[a,h]anthracene-induced subcutaneous tumors and expression of the Ahb allele, i.e. presence of the high-affinity Ah receptor and therefore readily inducible P1-450.
在C57BL/6J（Ahb/Ahb）、（C57BL/6J）（DBA/2J）F1（Ahb/Ahd）和（Ahd/Ahd）小鼠中，研究了Ah位点与二苯并[a,h]蒽和二苯并[a,c]蒽诱导皮下纤维肉瘤之间的关系。Ahb/Ahb和Ahb/Ahd小鼠具有高亲和力的Ah受体，因此多环烃诱导的芳烃羟化酶活性（细胞色素P1 - 450）很容易进行；Ahd/Ahd小鼠具有低亲和力的Ah受体，这种诱导过程进行得较差，至少相差10倍。二苯并[a,c]蒽被证明是一种相对较弱的致癌物，在每只小鼠高达300微克的剂量下，肿瘤发生率低于3%。相比之下，二苯并[a,h]蒽在Ahb/Ahb和Ahb/Ahd小鼠中引起近50%的肿瘤发生率，而在Ahd/Ahd小鼠中引起约2%的肿瘤发生率。两种异构体都能与胞质Ah受体紧密结合，并且这两种化学物质都能在Ahb/Ahb和Ahd/Ahd动物中诱导芳烃羟化酶活性。在（C57BL/6J）（DBA/2J）F1与DBA/2J回交的后代中，100只Ahb/Ahd小鼠中有63只发生肿瘤，7个Ahd/Ahd小鼠中无一发生肿瘤。这些数据表明，对二苯并[a,h]蒽诱导的皮下肿瘤的易感性与Ahb等位基因的表达之间存在严格的相关性，即存在高亲和力的Ah受体，因此P1 - 450易于诱导。
