Polychlorinated dibenzo-p-dioxins and dibenzofurans: Correlation between in vivo structure-activity relationships (SARs)
Polychlorinated dibenzofurans (PCDFs) and dibenzo-p-dioxins (PCDDs) elicit a number of common biologic and toxic responses which are triggered by their initial binding to a cytosolic receptor protein. These effects include the induction of several cytochrome P-448 dependent monoxygenases (eg, aryl hydrocarbon hydroxylase, AHH), body weight loss and thymic atrophy. The dose-response effects of selected PCDFs on AHH induction in rat hepatoma H-4-II E cells and cytosolic receptor binding affinities have been determined. The results of these in vivo and in vitro studies demonstrate the remarkable effects of structure on the activity of PCDFs. A systematic study of each of the four different position for chlorine substitution in the dibenzofuran ring system showed that the toxic and biologic potencies of these compounds varied with respect to differential chlorine substitution at all four position, i.e. C-3(7) > C-2(8) >C-4(6) > C-1(9). In vitro SARs for PCDDs confirmed the importance of the lateral CI substituents and also showed that 1,2(or 6,7-) substituted PCDDs were more active than the corresponding 1,3-dichloro analogs. In addition, there were significant decreases in activity with increasing non-lateral CI substitution. The SARs for PCDFs were different from the PCDDs and this was directly related to the asymmetric structure of the former group of compounds.
- Research Organization:
- Texas A and M Univ., College Station, TX (USA)
- OSTI ID:
- 6757414
- Report Number(s):
- PB-90-265117/XAB; CNN: EPA-810995
- Resource Relation:
- Other Information: Pub. in Chemosphere, Vol. 15, No. 9-12, 1725-1731(1986)
- Country of Publication:
- United States
- Language:
- English
Similar Records
Biological effects of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in bald eagle (Haliaeetus leucocephalus) chicks
A new structure-activity model for Ah receptor binding. Polychlorinated dibenzo-p-dioxins and dibenzofurans
Related Subjects
BENZOFURANS
STRUCTURE-ACTIVITY RELATIONSHIPS
DIOXIN
DOSE-RESPONSE RELATIONSHIPS
ENZYME INDUCTION
HEPATOMAS
IN VITRO
IN VIVO
MIXED-FUNCTION OXIDASES
RATS
RECEPTORS
TOXICITY
TUMOR CELLS
ANIMAL CELLS
ANIMALS
DISEASES
ENZYMES
FURANS
GENE REGULATION
HETEROCYCLIC COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
OXYGENASES
PROTEINS
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology