Effects of chlorinated benzenes of the activities of delta-aminolevulinic acid synthetase and heme oxygenase and on the content of hemoprotein in the liver of rats.

Abstract

Effects of chlorinated benzenes on the activities of delta-aminolevulinic acid (delta-ALA) synthetase and heme oxygenase, the rate-limiting enzyme in heme biosynthesis and degradation respectively, and on the incorporation of 3H-delta-ALA into hemoprotein in the liver of male rats were investigated. Monochlorobenzene (MCB) and 1,2,4-trichlorobenzene(TRCB) stimulated significantly the activities of above both hepatic enzymes. After a single injection of 200 mg/kg, heme oxygenase activity was enhanced rapidly and sustained markedly for at least 48 hr by MCB treatment, while that was also enhanced but restored nearly to control levels at 48 hr by TRCB. delta-ALA synthetase activity was once decreased at 6 hr and restored within 12 hr and then reached peak levels (about 2--3 times to control levels) at 24 hr by MCB or TRCB treatment. However, this activity was sustained for 48 hr by TRCB treatment, whereas returned again to nearly control levels by MCB at 48 hr. Cytochrome P-450 content at 48 hr was significantly decreased by MCB (63% to control), in contrast, increased by TRCB (200% to control). When MCB or TRCB injected once daily throughout the study, biphasic disappearance of radioactivity incorporated into CO-binding particles was shown in control and MCB- or TRCB-treated rats. The half-life of the fast phase was about 8 hr in control and about 6 or 13 hr in MCB- or TRCB-treated rats respectively.