Effect of nitro-substitution of environmental polycyclic aromatic hydrocarbons on activities of hepatic phase II enzymes in rats
- National Center for Toxicological Research, Jefferson, AR (USA)
A series of environmentally occurring nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) including those containing nitro-groups oriented coplanarly to the aromatic rings, such as 1- and 3-nitrobenzo(a)pyrene (1- and 3-NBAP), 6-nitrochrysene, and 1- and 4-nitropyrene, and those with a molecular orientation of the nitro-groups perpendicular to the aromatic moieties, such as 7-nitrobenz(a)anthracene and 6-nitrobenzo(a)pyrene (6-NBAP), were used to study the induction of certain rat hepatic phase II conjugating enzymes. Effects of these two different classes of nitro-PAHs on microsomal UDP-glucuronyltransferase (UDPGT), cytosolic glutathione S-transferases (GSTs) and sulfotransferases (STs) were investigated. After three consecutive daily i.p. injections, 1- and 3-NBAP and 6-nitrochrysene significantly increased the activities of UDPGT and GST, whereas their parent PAHs did not induce UDPGT (and GST activity was also unaltered by benzo(a)pyrene). UDPGT and GST activities were also significantly increased by 1-nitropyrene. In contrast, the sulfotransferases directed to 2-naphthol were not significantly induced by any PAH or nitro-PAH when assayed at either pH 5.5 or 7.5; however, the activities of aryl STs III and IV (pH 5.5) were significantly decreased following treatment with pyrene and two nitro-compounds, 6-NBAP and 7-nitrobenz(a)anthracene, in which the nitro-group is oriented perpendicular to the aromatic moiety. These results indicate that a coplanar orientation of the nitro-group of certain nitrated PAHs facilitates the induction of hepatic phase II enzymes by these compounds in rats, and the comparable induction patterns for P450IA1, UDPGT, and GST provide further evidence supporting the coordinate regulation (through the Ah receptor) of these phase I and phase II activities.
- OSTI ID:
- 6905398
- Journal Information:
- Drug and Chemical Toxicology; (USA), Vol. 12:3-4; ISSN 0148-0545
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
NITRO COMPOUNDS
TOXICITY
POLYCYCLIC AROMATIC HYDROCARBONS
TRANSFERASES
ENZYME INDUCTION
BENZOPYRENE
ENVIRONMENTAL EXPOSURE
LIVER
MICROSOMES
RATS
ANIMALS
AROMATICS
BODY
CELL CONSTITUENTS
CONDENSED AROMATICS
DIGESTIVE SYSTEM
ENZYMES
GENE REGULATION
GLANDS
HYDROCARBONS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
RIBOSOMES
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology