Black H S, Okotie-Eboh G, Gerguis J, Urban J I, Thornby J I
Veterans Affairs Medical Center, Houston, TX 77030, USA.
Photochem Photobiol. 1995 Dec;62(6):964-9. doi: 10.1111/j.1751-1097.1995.tb02394.x.
Previous studies have shown that a high level of dietary lipid (corn oil) exacerbates UV-carcinogenic expression in hairless mice. Furthermore, it was demonstrated that this effect occurs at the postinitiation, or promotion, stage of UV-carcinogenesis--a stage believed to be modulated immunologically. Thus, we sought to examine the influence of dietary lipid on specific immune parameters at various times within a UV-carcinogenic protocol, with the purpose of detecting potential relationships to UV carcinogenesis. Hairless mice were fed either a high- (12%, wt/wt, corn oil) or low-fat (0.75%, wt/wt, corn oil) diet for 2 weeks prior to start of the UV or experimental protocols. Animals were sensitized to dinitrochlorobenzene (DNCB) hapten and delayed-type hypersensitivity (DTH) was assessed. Delayed-type hypersensitivity was significantly suppressed (P = 0.01) in the high-fat group, even before UV irradiation. Although both groups exhibited UV-induced suppression of this response, the high-fat group was totally suppressed after 3 weeks of UV, whereas the low-fat group exhibited reactivity through week 8. The splenic T-lymphocyte (Thy 1.2+) population had declined by about 50% at the time of UV termination (11 weeks). Dietary lipid exerted no apparent influence upon this T-cell population. However, after 6 weeks of UV, I-J+ cells (a marker shown to be acquired adaptively by suppressor T lymphocytes) began to increase. By week 15 (4 weeks post-UV) I-J+ cells had increased by about 65% in the high-fat group, twice the % increase that occurred in the low-fat group. When UV-induced tumors were transplanted to recipient animals receiving various periods (0, 6, 11 weeks) of UV irradiation, no significant differences in median tumor rejection times between the two dietary groups occurred at 0 or 6 weeks. After 11 weeks of UV, the low-fat group exhibited a tumor rejection time that was comparable to that of nonirradiated animals, i.e. 21 days. However, median tumor rejection time for the high-fat group was greater than 63 days, significantly (P = 0.01) longer than that of the low-fat group. Thus, suppression of tumor rejection by high fat occurred at a time when high fat had been shown to exacerbate carcinogenic expression and when I-J+ cells had markedly increased. These data demonstrate that level of dietary lipid modulates immunoresponsiveness in UV-irradiated animals and is compatible with the thesis that immune suppression may account for the exacerbation of carcinogenic expression elicited by high dietary fat.
以往的研究表明，高含量的膳食脂质（玉米油）会加剧无毛小鼠的紫外线致癌表达。此外，已证明这种作用发生在紫外线致癌作用的起始后或促进阶段——这一阶段被认为是由免疫调节的。因此，我们试图在紫外线致癌方案的不同时间点研究膳食脂质对特定免疫参数的影响，目的是检测与紫外线致癌作用的潜在关系。在开始紫外线照射或实验方案前2周，给无毛小鼠喂食高（12%，重量/重量，玉米油）或低脂肪（0.75%，重量/重量，玉米油）饮食。动物用二硝基氯苯（DNCB）半抗原致敏，并评估迟发型超敏反应（DTH）。即使在紫外线照射前，高脂肪组的迟发型超敏反应也受到显著抑制（P = 0.01）。虽然两组均表现出紫外线诱导的这种反应抑制，但高脂肪组在紫外线照射3周后完全被抑制，而低脂肪组在第8周仍表现出反应性。在紫外线照射结束时（11周），脾脏T淋巴细胞（Thy 1.2+）群体减少了约50%。膳食脂质对该T细胞群体没有明显影响。然而，在紫外线照射6周后，I-J+细胞（一种已被证明可被抑制性T淋巴细胞适应性获得的标志物）开始增加。到第15周（紫外线照射后4周），高脂肪组的I-J+细胞增加了约65%，是低脂肪组增加百分比的两倍。当将紫外线诱导的肿瘤移植到接受不同时期（0、6、11周）紫外线照射的受体动物时，在0或6周时，两个饮食组之间的肿瘤中位排斥时间没有显著差异。在紫外线照射11周后，低脂肪组的肿瘤排斥时间与未照射动物相当，即21天。然而，高脂肪组的肿瘤中位排斥时间大于63天，明显（P = 0.01）长于低脂肪组。因此，高脂肪对肿瘤排斥的抑制发生在高脂肪已被证明会加剧致癌表达且I-J+细胞明显增加的时候。这些数据表明，膳食脂质水平调节紫外线照射动物的免疫反应性，并且与免疫抑制可能是高膳食脂肪引起致癌表达加剧的原因这一论点相符。
