Microsomes induction

PBBs strongly induced hepatic enzyme activity in pre-weaned rats, even at very low levels (0.2 pg/g>0.2ppb) independently of whether PBB exposure was pre- or postnatal (ref. 80, pp. 443-444). Dams were also affected, but to a lesser degree. Pups suckled by dams exposed to 10ppm PBB exhibited mixed-type microsomal induction of liver... 

Comtey, A.H, (1967). Pharmacological implications of microsomal induction. Plumnacoi. Rev. 19, 317-366. 

Chaney RL, Stoewsand GS, Bache CA, et al. 1978. Cadmium deposition and hepatic microsomal induction in mice fed lettuce grown on municipal sludge-amended soil. J Agric Food Chem 26 992-994. 

The toxicity of dimethoate to mice may be increased by pre-treatment with phenobarbitone [58] or pentobarbitone [59], whereas the toxicities of phos-phamidon, dicrotophos and their Ai-dealkylated derivatives are decreased [58]. Dimethoate requires oxidative activation, yet the vinyl phosphates do not. In vitro studies confirm the induction of mouse hepatic microsomal enzymes by phenobarbitone pre-treatment, which activate schradan, mala-thion and parathion [60]. Microsomal induction by pre-treatment with pentobarbitone stimulates not only the activation of certain organophos-phates, but also their catabolism, thereby reducing their toxicity, for example mipafox [59]. 

Rat Liver microsomes Induction of DMN demethylase by acetone and isopropanol 431... 

Rat, mouse Liver microsomes Induction by PB and 3-MC effects of induction on metabolism, mutagenicity, and carcinogenicity compared 136... 

Den Tonkelaar EM, Van Esch GJ. 1974. No-effect levels of organochlorine pesticides based on induction of microsomal liver enzymes in short-term toxicity experiments. Toxicology 2 371-380. 

Conney, A.H. (1982). Induction of Microsomal-Enzymes by Foreign Chemicals and Carcinogenesis by Polycyclic Aromatic-Hydrocarbons—Clowes, G.H.A. Memorial Lecture. Cancer Research 42, 4875 917. 

Polyphenols and flavanoids in rat liver microsomal fractions have been demonstrated to inhibit glucuronidation of estrone and estradiol in vitro (Zhu et al, 1998). In addition, flavonoids have also been found to induce phase I and II enzymes in rats including UDP-glucuronosyl transferase (Seiss et al, 1996). However, the effects of phytoestrogens have not been evaluated for either their inhibition or induction of glucuronosyl transferase activity. 

As noted above, many of the AEDs induce hepatic microsomal enzyme systems and thus reduce the effectiveness of hormonal contraceptives. Women taking AEDs that may reduce the effectiveness of hormonal contraceptives should be encouraged to also use other forms of birth control. Due to induction or inhibition of sex hormone metabolism and changes in binding of hormones to sex hormone binding globulin, some AEDs may reduce fertility. For example, valproate has been associated with a drug-induced polycystic ovarian syndrome. Women who experience difficulties with fertility should seek the advice of health care professionals with expertise in fertility. 

Parkinson, A., Thomas, P.E., Ryan, D.E. etal. (1983) Differential time course of induction of rat liver microsomal cytochrome P 450 isozymes and epoxide hydrolase by Aroclor 1254. Archives of Biochemistry and Biophysics, 225, 203-215. 

Figure 3. Induction of mutation in Sj typhimurium TA98 by BP-7,8-dihydrodiol, arachidonic acid, and ram seminal vesicle microsomes. Concentration dependence on BP-7,8-dihydro-diol. (Reproduced with permission from Ref. 22. Copyright 1978 Academic.)...

Saito et al. (134) found that the cytosolic nitroreductase activity was due to DT-diaphorase, aldehyde oxidase, xanthine oxidase plus other unidentified nitroreductases. As anticipated, the microsomal reduction of 1-nitropyrene was inhibited by 0 and stimulated by FMN which was attributed to this cofactor acting as an electron shuttle between NADPH-cytochrome P-450 reductase and cytochrome P-450. Carbon monoxide and type II cytochrome P-450 inhibitors decreased the rate of nitroreduction which was consistent with the involvement of cytochrome P-450. Induction of cytochromes P-450 increased rates of 1-aminopyrene formation and nitroreduction was demonstrated in a reconstituted cytochrome P-450 system, with isozyme P-448-IId catalyzing the reduction most efficiently. 

Matheson et al. (1978) reported the results of a battery of in vivo and in vitro assays to assess the genotoxicity of 1,1-dimethylhydrazine. Included were the Ames Salmonella microsome assay, a microbial suspension assay, mutation induction at the TK locus in L5178Y mouse lymphoma cells, stimulation of UDS in WI-38 cells, and a dominant lethal assay in mice. 1,1-Dimethylhydrazine was active in all of the tests except the dominant lethal assay. 

Interactive effects of PCBs on the induction of rat (Rattus sp.) liver microsomal cytochrome P-450c... 

Sunderman, F.W., Jr., M.C. Reid, L.M. Bibeau, and J.V. Linden. 1983. Nickel induction of microsomal heme oxygenase activity in rodents. Toxicol. Appl. Pharmacol. 68 87-95. 

Oikari, A. and B. Jimenez. 1992. Effects of hepatotoxicants on the induction of microsomal monooxygenase activity in sunfish liver by beta-naphthoflavone and benzo[a]pyrene. Ecotoxicol. Environ. Safety 23 89-102. 

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