Effects of diethyl maleate on aryl hydrocarbon hydroxylase and on 3-methyl-cholanthrene-induced skin tumorigenesis in rats and mice.
Topical administration of diethyl maleate (DEM) and L-methionine sulfoximine (MS) reduced the L-glutathione (GSH) levels in kidneys, livers, and skin of inbred BALB/c mice. Topical administration of DEM to BALB/c mice also increased the latency period before development of skin tumors that were induced by 3-methylcholanthrene painting. Similar treatment with MS also increased the latency period, though the delay was not as striking as that observed after DEM administration. Furthermore, DEM, which was believed to be specific in its action in reducing tissue GSH, was also capable of inhibiting aryl hydrocarbon hydroxylase (AHH) both in vitro and in vivo. Cyclohexene sulfide, another "specific" inhibitor of GSH transferase, inhibited AHH activity as well. Accordingly, the blockade of AHH by DEM may have been partly responsible for the increased latency time in the skin tumorigenesis experiments.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000494:pharmacology*; D008717:Methionine Sulfoximine / Q000494:pharmacology; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000209:etiology; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology*; D013997:Time Factors
D008298:Maleates; D008717:Methionine Sulfoximine; D008748:Methylcholanthrene; D001189:Aryl Hydrocarbon Hydroxylases; D005978:Glutathione