Animal studies addressing the carcinogenicity of TCDD (or related compounds) with an emphasis on tumour promotion
作者:
Yvonne P. Dragan,
Dieter Schrenk,
期刊:
Food Additives & Contaminants
(Taylor Available online 2000)
卷期:
Volume 17,
issue 4
页码: 289-302
ISSN:0265-203X
年代: 2000
DOI:10.1080/026520300283360
出版商: Taylor & Francis Group
关键词: Bioassays Carcinogenicity Neoplasms Tumour Promotion
数据来源: Taylor
摘要:
Dioxin and certain structurally related compounds increase the incidence of liver neoplasms in rodents upon chronic bioassay. Short-term studies indicate the lack of direct DNA-damaging effects including covalent binding to DNA; however, secondary mechanisms may be important in the observed carcinogenicity as these chemicals affect a number of pathways necessary for maintenance of normal growth control and differentiation status. Studies with TCDD in the mouse skin support a lack of initiating activity but an ability to promote the growth of previously initiated lesions indicative of a promoting agent. Mouse skin tumour promotion studies indicate that Ah receptor activation may be involved in promotion by TCDD and selected structurally related compounds. While the mechanism of carcinogenicity induced by TCDD is unknown, the processes involved have a no-effect level, which in the rat liver is at an exposure level below 10 ng TCDD/kg/ day. At least for the rodent liver, the relative effective dose for cytochrome P450 induction is not a good indicator of promotion potency. Studies on liver tumour promotion in the female rat liver support a nongenotoxic mechanism for the induction of neoplasms by TCDD. The ability of TCDD to enhance proliferation and inhibit apoptotic processes in focal hepatic lesions further supports an indirect mechanism of carcinogenicity.
点击下载:
PDF (249KB)
返 回