Prostaglandin synthetase dependent activation of 7,8-dihydro-7,8-dihydroxy-geno (a) pyrene to mutagenic derivativies

Marnett, L.J.; Reed, G.A.; Dennison, D.J.

Biochemical and Biophysical Research Communications 82(1): 210-216

1978


ISSN/ISBN: 0006-291X
PMID: 96834
DOI: 10.1016/0006-291x(78)90597-1
Accession: 068520641

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Abstract
The combination of arachidonic acid and a Tween 20 solubilized enzyme preparation from sheep seminal vesicles converts 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene to derivatives strongly mutagenic to Salmonella typhimurium tester strain TA 98. Under similar conditions no activation of benzo(a)pyrene, 4,5,-dihydro-4,5-dihydroxy-benzo(a)pyrene or 9,10-dihydro-9,10-dihydroxy-benzo(a)pyrene occurs. The activation of 7,8-dihydro-7,8-dihydroxy-benzo(a)pyrene is markedly reduced by the omission of arachidonic acid and is inhibited by the prostaglandin synthetase inhibitor indomethacin. 100 .mu.M butylated hydroxyanisole is also an effective inhibitor. This is the 1st report of the metabolic activation of 7,8-dihydro-7,8-dihydroxy-benzo(a)pyrene by an enzyme system distinct from the mixed-function oxidases.