FVB N MICE - AN INBRED STRAIN SENSITIVE TO THE CHEMICAL INDUCTION OF SQUAMOUS-CELL CARCINOMAS IN THE SKIN

FVB N MICE - AN INBRED STRAIN SENSITIVE TO THE CHEMICAL INDUCTION OF SQUAMOUS-CELL CARCINOMAS IN THE SKIN
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DOI:
10.1093/carcin/14.11.2353
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发表时间:
1993-11-01
期刊:
影响因子:
4.7
通讯作者:
YUSPA, SH
YUSPA, SH
中科院分区:
医学2区
文献类型:
--
作者:
HENNINGS, H;GLICK, AB;YUSPA, SH

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广泛使用FVB/N小鼠建立含有活性癌基因的转基因系,表明检测亲本FVB/N小鼠对实验性癌变的敏感性的重要性。用7,12-二甲基苯[a]蒽(DMBA)单次处理小鼠皮肤,并每周应用20次12- o -十四烷醇-13-乙酸酯(TPA)促进后,比较FVB/N小鼠、TPA敏感小鼠(senar和CD-1)和TPA耐药小鼠(BALB/c和C57BL/6)的皮肤肿瘤发生率。在FVB/N小鼠中,首先注射25杯DMBA,然后再注射低剂量TPA(2杯/周),仅25%的小鼠产生了一个或多个乳头状瘤,而senar小鼠为100%,CD-1小鼠为53%,BALB/c小鼠为17%,C57BL/6小鼠为0%。在TPA更有效的剂量下(5杯/周),FVB/N小鼠被5、25或100杯DMBA诱导,每只小鼠产生3.4、6.9和11.8个乳头瘤。相比之下,鳞状细胞癌(SCCs)(17-18/30小鼠)的发病率没有随着DMBA剂量的增加而增加。TPA促进非启动小鼠仅诱导6个乳头状瘤,但3个进展为SCCs,恶性转化率高。每周用10杯DMBA治疗20次的皮肤肿瘤诱导很少产生乳头瘤,但在FVB/N小鼠中,50.0%的乳头瘤进展为癌,而在senar中为9.15%,在CD-1中为37.5%,在BALB/c中为23.1%,在C57CL/6小鼠中为15.0%。FVB/N小鼠在14周、senar小鼠在24周、CD-1和C57BL/6小鼠在26周、BALB/c小鼠在34周出现第一次癌。因此,FVB/N小鼠在重复DMBA、DMBA启动- TPA促进甚至单独TPA治疗后,SCCs的发病率异常高。
The widespread use of FVB/N mice for the establishment of transgenic lines containing active oncogenes suggested the importance of testing the parent FVB/N mice for sensitivity to experimental carcinogenesis. After initiation of mouse skin by a single treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by 20 weekly applications of 12-O-tetradecanoylphorbol-13-acetate (TPA), the skin tumor incidence was compared in FVB/N mice, TPA-sensitive (SENCAR and CD-1) and TPA-resistant mice (BALB/c and C57BL/6). Initiation by 25 mug DMBA followed by promotion with a low dose of TPA (2 mug/week) induced one or more papillomas in only 25% of FVB/N mice, compared with 100% in SENCAR, 53% in CD-1, 17% in BALB/c and 0% in C57BL/6 mice. At a more effective dose of TPA (5 mug/week), FVB/N mice initiated by 5, 25 or 100 mug DMBA developed 3.4, 6.9 and 11.8 papillomas per mouse. In contrast, the incidence of squamous cell carcinomas (SCCs) (17-18/30 mice) did not increase with DMBA dose. TPA promotion of non-initiated mice induced only six papillomas, but three progressed to SCCs, a high rate of malignant conversion. Skin tumor induction by 20 weekly treatments with 10 mug DMBA produced few papillomas, but 50.0% of the papillomas progressed to carcinomas in FVB/N mice, compared with 9.15% in SENCAR, 37.5% in CD-1, 23.1% in BALB/c and 15.0% in C57CL/6 mice. The first carcinomas appeared after 14 weeks in FVB/N, 24 weeks in SENCAR, 26 weeks in CD-1 and C57BL/6 and 34 weeks in BALB/c mice. Thus, FVB/N mice develop an unusually high incidence of SCCs after treatment with repeated DMBA, DMBA initiation - TPA promotion and even TPA alone.