Moon R C, Rao K V, Detrisac C J
IIT Research Institute, Chicago, IL 60616.
Res Rep Health Eff Inst. 1990 Apr(32):1-29.
The carcinogenic potential of 1-nitropyrene, a major mutagenic constituent of diesel-exhaust particles, was investigated using a hamster respiratory-carcinogenesis model. The specific aims of the investigation were to assess the activity of 1-nitropyrene as a complete carcinogen (Study 1) and as a cocarcinogen (Study 2) when administered in combination with the known environmental carcinogen benzo[a]pyrene. Preparations of 1-nitropyrene and benzo[a]pyrene adsorbed onto an equal mass of carbon carrier particles (Stokes diameter 2 to 5 microns, greater than 70 percent) were used for the intratracheal administration. Evaluation of 1-nitropyrene as a complete carcinogen involved exposing male Syrian golden hamsters to 1 or 2 mg of 1-nitropyrene either once or twice each week. A once-per-week instillation of 2 mg of benzo[a]pyrene served as a positive control. Two groups of animals received sterile saline only (saline controls) or carbon particles suspended in saline (particle controls). In addition, a group of untreated hamsters served as shelf controls. Evaluation of 1-nitropyrene as a cocarcinogen involved treating animals once each week with either 1 or 2 mg of 1-nitropyrene with or without concomitant exposure to 0.25 mg of benzo[a]pyrene. The studies were terminated after 92 weeks of treatment. In both studies, hamsters receiving 1-nitropyrene showed a dose-related decrease in survival and body-weight gain. In general, animals in Study 2 showed better survival than those in Study 1. A high intercurrent mortality was observed in the control groups of Study 1. In order to adjust for intercurrent mortality, tumor incidences were analyzed after modeling (using Cox regression) the effect of treatment in all animals for the period they were alive. A broad spectrum of neoplastic and nonneoplastic lesions was observed in the lungs and tracheas of all hamsters except shelf controls. Because of the histologic complexity of these lesions, the slides were coded, and the tissues were evaluated by an unbiased pathologist. The tumor types included papillomas, adenomas, adenocarcinomas, and squamous cell carcinomas, the latter being the most prevalent type in benzo[a]pyrene-treated animals. In view of the low incidence of tumors in 1-nitropyrene-treated hamsters, the tumor incidences in various experimental groups were compared regardless of the tumor type, location, and multiplicity. A small, but significant, increase in tumor incidence, with a dose-response trend, was observed only in Study 2 hamsters receiving 1-nitropyrene once weekly. In contrast, treatment with benzo[a]pyrene adsorbed onto carbon particles induced benign and malignant tumors virtually in all animals that survived more than 50 weeks of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
利用仓鼠呼吸道致癌模型，对柴油废气颗粒的主要诱变成分1-硝基芘的致癌潜力进行了研究。该研究的具体目标是评估1-硝基芘作为完全致癌物（研究1）以及与已知环境致癌物苯并[a]芘联合使用时作为促癌剂（研究2）的活性。将1-硝基芘和苯并[a]芘吸附到等质量的碳载体颗粒（斯托克斯直径2至5微米，大于70%）上的制剂用于气管内给药。评估1-硝基芘作为完全致癌物包括每周一次或两次让雄性叙利亚金仓鼠接触1或2毫克1-硝基芘。每周一次滴注2毫克苯并[a]芘作为阳性对照。两组动物仅接受无菌生理盐水（生理盐水对照组）或悬浮在生理盐水中的碳颗粒（颗粒对照组）。此外，一组未处理的仓鼠作为饲养对照组。评估1-硝基芘作为促癌剂包括每周一次用1或2毫克1-硝基芘处理动物，同时或不同时接触0.25毫克苯并[a]芘。治疗92周后终止研究。在两项研究中，接受1-硝基芘的仓鼠在生存率和体重增加方面均出现剂量相关的下降。总体而言，研究2中的动物比研究1中的动物生存率更高。在研究1的对照组中观察到较高的并发死亡率。为了校正并发死亡率，在对所有动物存活期间的治疗效果进行建模（使用Cox回归）后分析肿瘤发生率。在所有仓鼠（饲养对照组除外）的肺和气管中观察到广泛的肿瘤性和非肿瘤性病变。由于这些病变的组织学复杂性，对切片进行了编码，并由一位无偏见的病理学家对组织进行评估。肿瘤类型包括乳头状瘤、腺瘤、腺癌和鳞状细胞癌，后者是苯并[a]芘处理动物中最常见的类型。鉴于1-硝基芘处理的仓鼠中肿瘤发生率较低，对各个实验组的肿瘤发生率进行了比较，而不考虑肿瘤类型、位置和数量。仅在研究2中每周接受一次1-硝基芘的仓鼠中观察到肿瘤发生率有小幅但显著的增加，并呈现剂量反应趋势。相比之下，用吸附在碳颗粒上的苯并[a]芘处理几乎在所有存活超过50周的动物中都诱发了良性和恶性肿瘤。（摘要截断于400字）
