Animal studies addressing the carcinogenicity of TCDD (or related compounds) with an emphasis on tumour promotion

Citation
Yp. Dragan et D. Schrenk, Animal studies addressing the carcinogenicity of TCDD (or related compounds) with an emphasis on tumour promotion, FOOD ADDIT, 17(4), 2000, pp. 289-302
Citations number
84
Categorie Soggetti
Food Science/Nutrition
Journal title
FOOD ADDITIVES AND CONTAMINANTS
ISSN journal
0265203X → ACNP
Volume
17
Issue
4
Year of publication
2000
Pages
289 - 302
Database
ISI
SICI code
0265-203X(200004)17:4<289:ASATCO>2.0.ZU;2-M
Abstract
Dioxin and certain structurally related compounds increase the incidence of liver neoplasms in rodents upon chronic bioassay,. Short-term studies indi cate the lack of direct DNA-damaging effects including covalent binding To DNA; however, secondary, mechanisms may be important in the observed carcin ogenicity as these chemicals affect a number of pathways necessary for main tenance of normal growth control and differentiation status. Studies with T CDD in the mouse skin support a lack of initiating activity but an ability to promote the growth of previously initiated lesions indicative of a promo ting agent. Mouse skin tumour promotion studies indicate that Ah receptor a ctivation may be involved in promotion by TCDD and selected structurally re lated compounds. While the mechanism of carcinogenicity induced by TCDD is unknown, the processes involved have a no-effect level, which in the rat li ver is at an exposure level below 10 ng TCDD/kg/ day. At least for the rode nt 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 inhibi t apoptotic processes in focal hepatic lesions further supports an indirect mechanism of carcinogenicity.