Effects of separate and combined treatments with gamma radiation and diethylnitrosamine in neonatal rats on the induction of altered hepatocyte foci and hepatic tumors.
Effects of separate and combined treatments with gamma radiation and diethylnitrosamine in neonatal rats on the induction of altered hepatocyte foci and hepatic tumors.
复制标题
伽马射线和二乙基亚硝胺单独和联合治疗对新生大鼠肝细胞病灶改变和肝肿瘤诱导的影响。
DOI：
10.1093/carcin/8.4.599
复制
发表时间：
1987
期刊：
影响因子：
4.7
通讯作者：
Carnes,BA
中科院分区：
文献类型：
--
作者：
Peraino,C;Grdina,DJ;Staffeldt,EF;Russell,JJ;Prapuolenis,A;Carnes,BA
为了表征γ射线和二乙基亚硝胺（DEN）联合治疗对诱导组织化学可检测的肝细胞病灶和肝肿瘤的影响，我们评估了150日龄大鼠肝脏中这些病灶的产量，这些大鼠接受了单剂量γ射线（75红色，全身）和i. p. -注射DEN（0.15 μmol/g体重），单独或组合。联合治疗涉及以两种可能的顺序给予两种刺激，治疗间隔设定为1小时。检查病灶人群的两种组织化学标志物（γ-谷氨酰转肽酶[GGT（+）]和铁排斥[FE（−）]升高，产生三种可检测的病灶表型，即GGT（+）病灶、FE（−）病灶和GGT（+）、FE（−）病灶。通过使用连续冰冻切片技术和计算机辅助图像分析来定量这三种表型的频率。GGT（+）病灶诱导通过联合治疗协同增强，无论两种刺激的给药顺序如何;其余两种表型未显示出这种增强。当治疗顺序为γ → DEN时，GGT（+）病灶反应的幅度显著大于DEN → γ。无论γ-DEN治疗顺序如何，接受γ-DEN联合治疗的大鼠的肿瘤产量与单独接受DEN的大鼠的肿瘤产量相似。这些结果表明：（i）表型上可区分的病变，包括具有不同组织化学标志物模式的病灶和肿瘤，起源于不同遗传位点的特定类型的损伤，并且是发育独立的;（ii）改变的肝细胞病灶中GGT（+）标志物的表达不是早期肝肿瘤的可靠指标。
To characterize the effects of combined treatments with gamma radiation and diethylnitrosamine (DEN) on the induction of histochemically detectable altered hepatocyte foci and hepatic tumors, we assessed the yields of these lesions in the livers of 150-day-old rats that had been treated neonatally with a single dose of gamma radiation (75 red, whole body) and i.p.-injected DEN (0.15 μmol/g body wt), either separately or in combination. The combined treatments involved the administration of the two stimuli in both possible sequences, with the interval between treatments set at 1 h. The focus population was examined for two histochemical markers (elevated gamma-glutamyl transpeptidase [GGT(+)J and iron exclusion [FE(−)], giving rise to three detectable focus phenotypes, i.e. GGT(+) foci, FE(−) foci, and GGT(+), FE(−) foci. Frequencies of the three phenotypes were quantitated through the use of serial frozen sectioning techniques and computer-assisted image analysis. GGT(+) focus induction was synergistkally enhanced by the combined treatment irrespective of the order in which the two stimuli were administered; the remaining two phenotypes did not show such enhancement. The magnitude of the GGT(+) focus response was significantly greater when the treatment sequence was gamma → DEN as opposed to DEN → gamma. Tumor yields in rats receiving combined gamma-DEN treatment were similar to those in rats receiving the DEN alone, irrespective of the gamma-DEN treatment sequence. These results suggest that (i) phenotypically distinguishable lesions, including foci with different histochemical marker patterns and tumors, originate from specific types of damage at different genetic loci and are developmentally independent; and (ii) the expression of the GGT(+) markerper sein altered hepatocyte foci is not a reliable index of incipient hepatic neoplasia.