PMID: 40390Aug 1, 1979

Mutagenic activation of tris(2,3-dibromopropyl)phosphate: the role of microsomal oxidative metabolism

Acta Pharmacologica Et Toxicologica
E J SøderlundE Dybing

Abstract

The flame retardant tris(2,3-dibromopropyl)phosphate (Tris-BP) is converted to products which are mutagenic for Salmonella typhimurium TA 100 in the presence of rat liver microsomes, NADPH and oxygen. Other bromopropyl-compounds were also mutagenic; 2,3-dibromopropene and 2,3-dibromopropionic acid were directly mutagenic, whereas 2,3-dibromopropanol and tris(2-bromopropyl)phosphate were weakly mutagenic after addition of liver microsomes and cofactors. Typical in vivo and in vitro inhibitors of cytochrome P-450 inhibited Tris-BP mutagenicity. The effects of inducers of cytochrome P-450 on Tris-BP mutagenicity was dependent on the concentration of mutagen and microsomal protein in the assay, indicating complexity in the kinetics involved when dealing with possible multiple pathways that lead to mutagenicity. Addition of glutathione strongly inhibited Tris-BP mutagenicity. It is suggested that Tris-BP is oxidized to a reactive electrophile, possibly the 2-keto derivative, which could react with nucleophilic groups in DNA and thus lead to mutagenic events.

References

Nov 7, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Steven M BryceStephen D Dertinger
Jan 1, 1984·Critical Reviews in Toxicology·G F RushJ B Hook
Oct 1, 1991·Journal of Applied Toxicology : JAT·K TakadaM Fukuoka
Sep 1, 1986·Cell Biology and Toxicology·E DybingS S Thorgeirsson
Jan 1, 1980·Environmental Mutagenesis·A M ChehR G McKinnell

Citations

Jun 1, 1978·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·C T BedfordD E Wiggins
Jan 7, 1977·Science·A Blum, B N Ames
Feb 1, 1976·Bulletin of Environmental Contamination and Toxicology·L E St JohnD J Lisk
Jul 1, 1975·Bulletin of Environmental Contamination and Toxicology·W H Gutenmann, D J Lisk
Nov 1, 1975·Biochemical Pharmacology·M D Stonard
Dec 15, 1972·Biochemical Pharmacology·M R Franklin
Feb 19, 1971·Biochemical and Biophysical Research Communications·T R Tephly, P Hibbeln
Nov 1, 1968·Biochemical Pharmacology·M W Anders
Jul 1, 1967·The Biochemical Journal·E Boyland, L F Chasseaud

Related Concepts

Cytochrome P-450 Oxygenase
Microsomes, Liver
1-Propanol
NADP
Propane
Organopyrophosphorus Compounds
Oxidation-Reduction
Flame Retardants
Clastogens
Salmonella typhimurium LT2

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