Chauvenet P H, Paque R E
Int J Cancer. 1982 Aug 15;30(2):187-92. doi: 10.1002/ijc.2910300210.
The effect of 200 micrograms doses of all-trans retinoic acid, given over a long duration (daily for 8 weeks, suspended for 3 weeks, then resumed daily for 4 weeks) or short duration (daily for 30 days), on the induction of fibrosarcomas in C57BL/6J mice by MCA was evaluated. A reduced level of carcinogenesis was observed with both lengths of retinoic acid treatment, since respective incidences of MCA fibrosarcomas were 63 and 61% of those in saline-treated controls. In other studies, the effect of all-trans retinoic acid on syngeneic growth of two experimental fibrosarcomas (B6 25 and B6 27, induced previously in C57BL/6J mice by MCA) was assessed. Retinoic-acid-treated mice were more resistant to higher doses of viable B6 27 (LD50 = 2.85) and especially B6 25 (LD50 = 3.80) than were corresponding saline- or corn-oil-treated controls (LD50 less than 2.0). The strength of resistance conferred by retinoic acid treatment thus varied considerably between these tumors, despite their common strain derivation and histopathological origin. Additional studies explored the effect on B6 27 growth of giving all-trans retinoic acid during either the sensitization or challenge stage of standard syngeneic immunogenicity tests. Mice given all-trans retinoic acid during sensitization displayed a markedly increased resistance to challenge with the immunospecific B6 27 tumor (LD50 = 5.30), compared to challenged controls that received saline (LD50 = 2.60) or corn-oil (LD50 = 2.55) during preimmunization. In contrast, when B6 27-preimmunized mice were treated with all-trans retinoic acid after challenge with homologous tumor, resistance to B6 27 (assessed by tumor growth rate and LD50 dose) was not increased but remained comparable to that of saline-or corn-oil-treated controls. While the mechanism(s) by which all-trans retinoic acid inhibits syngeneic growth of MCA tumors is unknown, our results support an immunostimulatory effect, evidenced by tumor resistance in both non-immune and specifically preimmunized syngeneic hosts.
评估了长时间（每日给药8周，停药3周，然后再每日给药4周）或短时间（每日给药30天）给予200微克剂量的全反式维甲酸对甲基胆蒽（MCA）诱导C57BL/6J小鼠发生纤维肉瘤的影响。两种维甲酸治疗时长均观察到致癌水平降低，因为MCA纤维肉瘤的各自发生率分别为盐水处理对照组的63%和61%。在其他研究中，评估了全反式维甲酸对两种实验性纤维肉瘤（B6 25和B6 27，先前由MCA在C57BL/6J小鼠中诱导产生）同基因生长的影响。与相应的盐水或玉米油处理对照组（半数致死量小于2.0）相比，维甲酸处理的小鼠对更高剂量的活B6 27（半数致死量 = 2.85）尤其是B6 25（半数致死量 = 3.80）更具抗性。尽管这些肿瘤具有共同的品系来源和组织病理学起源，但维甲酸处理赋予的抗性强度在这些肿瘤之间差异很大。额外的研究探讨了在标准同基因免疫原性试验的致敏或激发阶段给予全反式维甲酸对B6 27生长的影响。与在免疫前接受盐水（半数致死量 = 2.60）或玉米油（半数致死量 = 2.55）的激发对照组相比，在致敏期间给予全反式维甲酸的小鼠对免疫特异性B6 27肿瘤激发的抗性显著增加（半数致死量 = 5.30）。相反，当用同源肿瘤激发后用全反式维甲酸处理预先免疫B6 27的小鼠时，对B6 27的抗性（通过肿瘤生长速率和半数致死量剂量评估）并未增加，而是与盐水或玉米油处理对照组相当。虽然全反式维甲酸抑制MCA肿瘤同基因生长的机制尚不清楚，但我们的结果支持一种免疫刺激作用，这在非免疫和特异性预先免疫的同基因宿主中的肿瘤抗性中得到了证明。
