Cholanthrene, 20-methyl

PAHs, such as benzo[a]pyrene and 3-methyl cholanthrene, induce P450 lAl/2 (Chapter 2). 

There is evidence for immunosuppressive effects of PAHs in rodents (Davila et al. 1997). For example, strong immunosuppressive effects were reported in mice that had been dosed with benzo[fl]pyrene and 3-methyl cholanthrene, effects that persisted for up to 18 months (Environmental Health Criteria 202). Multiple immu-notoxic effects have been reported in rodents, and there is evidence that these result from disturbance of calcium homeostasis (Davila et al. 1997). PAHs can activate protein tyrosine kinases in T cells that initiate the activation of a form of phospholipase C. Consequently, release of inositol triphosphate—a molecule that immobilizes Ca + from storage pools in the endoplasmic reticulum—is enhanced. 

Figure 2. Views of some carcinogenic molecules showing K- and bay- regions. Views are given of BP (I), DMBA (II), 3-methyl-cholanthrene (III), ll-methyl-15,16-dihydrocyclopenta[a]phen-anthracene (VII) and 5-methylchrysene (VIII). These and all subsequent ball-and-stick diagrams were drawn using the computer program VIEW (141).

A potentially powerful probe for sorting out the contribution of hydroperoxide-dependent and mixed-function oxidase-dependent polycyclic hydrocarbon oxidation is stereochemistry. Figure 9 summarizes the stereochemical differences in epoxidation of ( )-BP-7,8-dihydrodiol by hydroperoxide-dependent and mixed-function oxidase-dependent pathways (31,55,56). The (-)-enantiomer of BP-7,8-dihydrodiol is converted primarily to the (+)-anti-diol epoxide by both pathways whereas the (+)-enantiomer of BP-7,8-dihydrodiol is converted primarily to the (-)-anti-diol epoxide by hydroperoxide-dependent oxidation and to the (+)-syn-diol epoxide by mixed-function oxidases. The stereochemical course of oxidation by cytochrome P-450 isoenzymes was first elucidated for the methycholanthrene-inducible form but we have detected the same stereochemical profile using rat liver microsomes from control, phenobarbital-, or methyl-cholanthrene-induced animals (32). The only difference between the microsomal preparations is the rate of oxidation. 

Neoplasms in several species of fishes have been produced experimentally with 3-methyl-cholanthrene, acetylaminofluorene, benzol a Ipyrcnc, and 7,12-dimethylbenz[a]anthracene, with tumors evident 3 to 12 months postexposure (Couch and Harshbarger 1985 Hendricks et al. 1985 Hawkins et al. 1989). Under laboratory conditions, liver neoplasms were induced in two species of minnows (Poeciliopsis spp.) by repeated short-term exposures (6 h once a week, for... 

Increased weight of liver, kidney, gall bladder, and spleen of sea catfish (Ariusfelis) by 3-methyl-cholanthrene, which was dose-related (Melius and Elam 1983)... 

Abnormal blood chemistry in oysters (Crassostrea virginica) exposed for 1 year to 5 pg 3-methyl-cholanthrene/L (Couch et al. 1983)... 

Bend, J.R., Pohl, R.J., Davidson, N.P. and Fouts, J.R. Response of hepatic and renal microsomal mixed-function oxidases in the little skate, Ra.ja erinacea, to pretreatment with 3-methyl-cholanthrene or TCDD (2,3,7,8-tetrachlorodibenzo- -dioxin). Bull. Mt, Desert Is. Biol. 

An NMR method has been used to determine the association constant of benzo[6]thiophene with the electron acceptors 1,4-dinitrobenzene and 1,3,5-trinitrobenzene in chloroform solution.118 The 1H NMR spectra of some sulfur analogs of cholanthrene and methyl-cholanthrene have been analyzed.119... 

Cl. Phenanthrene, 1,2-cyclopentenophenanthrene, 4,5-dimethyl-phenanthrenes, chrysene, octahydrochrysene, 20-methyl-cholanthrene, 1,2-dibenzanthracene, 9,10-dimethyl-1,2-dibenzanthracene, 1,2-5,6-dibenzanthracene, 1,2-7,8-dibenzacridine, and triphenylene. 

Although not necessarily a genotoxic event, in vitro cell transformation is included in this section. The basic fraction of a tryptophan pyrolysate and synthetic Trp-P-1 and Trp-P-2 were tested for transforming activity in Syrian golden hamster embryo cells (37). The percent of morphologically transformed colonies was 1.5, 1.3 and 0.54 for Trp-P-2, Trp-P-1 and 3-methyl-cholanthrene (3MC), respectively. The optimum concentrations for Trp-P-1 and Trp-P-2 were 0.5 pg/ml versus 1.0 pg/ml for 3MC. 

TCDD given 2 days prior to or concurrently with methylcholanthrene did not affect methyl-cholanthrene-induced carcinogenicity in C57BL/6 mice (Kouri et al. 1978) in contrast, 2,3,7,8-TCDD pretreatment (intraperitoneal or subcutaneous) of DBA/2 mice slightly increased the carcinogenic index. 

TBC 32 is present in human and cat urine, occurring in cat urine predominantly as the (5) enantiomer (64). TBC 32 is also found to be a major metabolite of the carboxylic acid 38 in rats, and it is excreted predominantly as the (S) enantiomer (65,66). Administration of TBC 29 to rats in the presence of 3-methyl-cholanthrene, which is an inducer of cytochrome P-450 enzymes, led to the formation of the novel metabolite TBC 33 with a hydroxy group at C-5 (66). 

The polycyclic aromatic hydrocarbons (PAHs) encompass a further group of environmental chemicals with antiestrogenic activity. Examples are benzo[a] pyrene, benz[a]anthracene, 3-methyl-cholanthrene, and 7,12-dimethylbenz[a] anthracene [120b]. 

For example, Cunninghamella elegans oxidizes benzo[a]pyrene to its 7,8-oxide, hydrates the 7,8-oxide to the 7,8-dihydrodiol, and metabolizes this as well as the 9,10-dihydrodiol to diol epoxides " with stereochemical consequences quite similar to those observed for liver microsomes from the 3-methyl-cholanthrene-treated... 

Conney AH, Miller EC, Miller JA. 1956. The metabolism of methylated aminoazo dyes. V. Evidence for induction of enzyme synthesis in the rat by 3-methyl-cholanthrene. Cancer Res. 16 450-59... 

Kuntzman R, Levin W, Schilling G, Alvares A. 1969. The effects of 3-methyl-cholanthrene and phenobarbital on liver microsomal hemoproteins and on the hy-droxylation of benzpyrene. In Microsomes and Drug Oxidations, ed. JR Gillette, AH Conney, GJ Cosmides, RW Estabrook, JR Fouts, GJ Mannering, pp. 349-69. New York Academic... 

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