Casale G P, Higginbotham S, Johansson S L, Rogan E G, Cavalieri E L
Eppley Institute for Research in Cancer, Department of Pathology and Microbiology, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, Nebraska 68198-6805, USA.
Fundam Appl Toxicol. 1997 Mar;36(1):71-8. doi: 10.1006/faat.1997.2291.
The potent carcinogenicity of dibenzo[a,l]pyrene in mouse skin is associated with an inflammation unique among polycyclic aromatic hydrocarbons and expressed as erythema. The time course of erythema and the associated histological events in the skin of female SENCAR mice were determined after a single application of 6.25-200 nmol dibenzo[a,l]pyrene or selected metabolites. Dibenzo[a,l]pyrene and dibenzo[a,l]pyrene-11,12-dihydrodiol, precursor to the bay-region diol epoxide, induced an erythema first present 5-6 days after treatment. Dibenzo[a,l]pyrene-8,9-dihydrodiol and other dibenzo[a, l]pyrene metabolites, however, did not induce erythema. These findings suggest a central role for the bay-region diol epoxide in the induction of the observed inflammation. The intensity and duration of erythema were dose-dependent, whereas the delayed appearance of erythema was constant and dose-independent. These results suggest induction of an immune hypersensitivity by dibenzo[a, l]pyrene and its 11,12-dihydrodiol. Histological changes in the skin were consistent with a contact hypersensitivity reaction and included, in association with erythema, epidermal hyperplasia and the presence of mononuclear leukocytes in the dermis. Animals were tested for dibenzo[a,l]pyrene-induced contact hypersensitivity. Female SENCAR mice were treated with a single dermal application of dibenzo[a,l]pyrene or 7,12-dimethylbenz[a]anthracene. Five days later, the animals were challenged with a single application of dibenzo[a,l]pyrene or 7,12-dimethylbenz[a]anthracene to the ear pinna. Ear swelling exhibited features of a contact hypersensitivity reaction, including (1) delayed appearance after challenge, (2) noninducibility in animals not previously exposed to chemical sensitizer, and (3) chemical specificity. The results suggest that dibenzo[a,l]pyrene induces, via its bay-region diol epoxide, a contact hypersensitivity reaction that may promote tumor development and thereby enhance carcinogenic potency.
二苯并[a,l]芘在小鼠皮肤中的强致癌性与多环芳烃中独特的炎症反应相关，表现为红斑。在单次涂抹6.25 - 200 nmol二苯并[a,l]芘或选定的代谢产物后，测定雌性SENCAR小鼠皮肤中红斑的时间进程以及相关的组织学变化。二苯并[a,l]芘和湾区二醇环氧化物的前体二苯并[a,l]芘-11,12-二氢二醇在处理后5 - 6天首次引发红斑。然而，二苯并[a,l]芘-8,9-二氢二醇和其他二苯并[a,l]芘代谢产物并未引发红斑。这些发现表明湾区二醇环氧化物在观察到的炎症诱导中起核心作用。红斑的强度和持续时间呈剂量依赖性，而红斑的延迟出现是恒定的且与剂量无关。这些结果表明二苯并[a,l]芘及其11,12-二氢二醇诱导了免疫超敏反应。皮肤的组织学变化与接触性超敏反应一致，包括与红斑相关的表皮增生以及真皮中单核白细胞的存在。对动物进行了二苯并[a,l]芘诱导的接触性超敏反应测试。雌性SENCAR小鼠单次经皮涂抹二苯并[a,l]芘或7,12-二甲基苯并[a]蒽。五天后，对动物的耳廓单次涂抹二苯并[a,l]芘或7,12-二甲基苯并[a]蒽进行激发。耳部肿胀表现出接触性超敏反应的特征，包括(1)激发后延迟出现，(2)在未预先接触化学致敏剂的动物中无法诱导，以及(3)化学特异性。结果表明，二苯并[a,l]芘通过其湾区二醇环氧化物诱导接触性超敏反应，这可能促进肿瘤发展，从而增强致癌效力。
