Susceptibility to effects of UVB radiation on induction of contact hypersensitivity as a risk factor for skin cancer in humans.

Susceptibility to effects of UVB radiation on induction of contact hypersensitivity as a risk factor for skin cancer in humans.
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DOI:
10.1111/1523-1747.ep12504877
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发表时间:
1990-11
期刊:
The Journal of investigative dermatology
影响因子:
--
通讯作者:
T. Yoshikawa;V. Rae;W. Bruins-Slot;J. V. D. Berg;J. Taylor;J. Taylor;J. Streilein
T. Yoshikawa;V. Rae;W. Bruins-Slot;J. V. D. Berg;J. Taylor;J. Taylor;J. Streilein
中科院分区:
其他
文献类型:
--
作者:
T. Yoshikawa;V. Rae;W. Bruins-Slot;J. V. D. Berg;J. Taylor;J. Taylor;J. Streilein

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正常、健康的人类志愿者和证实有非黑色素瘤皮肤癌病史的患者在臀部皮肤暴露于急性低剂量紫外线B (UVB)辐射后,对二硝基氯苯(DNCB)产生接触性超敏反应的能力进行了测试。使用一种辐射方案,几乎可以使辐照皮肤上正常的朗格汉斯细胞完全消失,当在辐照部位涂上2000微克的DNCB时,大约60%的健康志愿者出现了剧烈的接触性超敏反应(CH)。这些人被指定为uvb抗性,并与其他被指定为uvb易感的人区分开来,这些人在相同的治疗方案下没有出现接触性超敏反应。随后发现,几乎所有(92%)暴露于UVB和DNCB的皮肤癌患者都没有发生CH,即对UVB敏感。在随后的实验中,将2000微克DNCB涂抹在uvb易感个体未照射的皮肤上,进一步揭示了正常人和皮肤癌患者之间的差异。大约45%的后者(而前者没有)仍然无反应(在第二次致敏后未能发生接触性超敏反应),这意味着他们已经具有免疫耐受性。这些耐受性的个体对不相关的半抗原,二苯环倾向反应正常。我们得出的结论是,人类类似于近亲繁殖的实验室小鼠,因为有些人对uvb敏感,而另一些人则对uvb有抵抗力。由于uvb敏感性在皮肤癌患者中的发生率明显更高,并且特异性无反应性只能在这些患者中被证明,我们提出uvb敏感性,正如我们在这个半抗原系统中定义的那样,可能是皮肤癌发展的一个危险因素。
Normal, healthy human volunteers and patients with proved history of non-melanoma skin cancer have been tested for their capacity to develop contact hypersensitivity to dinitrochlorobenzene (DNCB) following exposure of buttock skin to acute, low-dose ultraviolet B (UVB) radiation. Using a radiation protocol that achieves virtually complete depletion of normal-appearing Langerhans cells from irradiated skin, it was learned that approximately 60% of healthy volunteers developed vigorous contact hypersensitivity (CH) when 2000 micrograms DNCB was painted on the irradiated site. These individuals were designated UVB-resistant, and were distinguished from other individuals, designated UVB-susceptible, who failed to develop contact hypersensitivity following an identical treatment protocol. It was then discovered that virtually all (92%) skin cancer patients exposed to UVB and DNCB failed to develop CH, i.e., were UVB-susceptible. In subsequent experiments, epicutaneous application of 2000 micrograms DNCB to unirradiated skin of UVB-susceptible individuals revealed a further distinction between normal persons and skin cancer patients. Approximately 45% of the latter (and none of the former) remained unresponsive (failed to develop contact hypersensitivity following this second attempt at sensitization), implying that they had been rendered immunologically tolerant. These tolerant individuals responded normally to the unrelated hapten, diphencyprone. We conclude that human beings resemble inbred strains of laboratory mice in that some individuals are UVB-susceptible, whereas others are UVB-resistant. Because the incidence of UVB-susceptibility was significantly higher in skin cancer patients, and as specific unresponsiveness could be demonstrated only in these patients, we propose that UVB-susceptibility, as we define it in this hapten system, may be a risk factor for the development of skin cancer.