Chrysenes carcinogenic activity

Horton AW, Christian GM. 1974. Cocarcinogenic versus incomplete carcinogenic activity among aromatic hydrocarbons Contrast between chrysenes and benzo[b]triphenylene. J Natl Cancer Inst 53 1017-1020. 

Methods for the synthesis of the biologically active dihydrodiol and diol epoxide metabolites of both carcinogenic and noncarcinogenic polycyclic aromatic hydrocarbons are reviewed. Four general synthetic routes to the trans-dihydrodiol precursors of the bay region anti and syn diol epoxide derivatives have been developed. Syntheses of the oxidized metabolites of the following hydrocarbons via these methods are described benzo(a)pyrene, benz(a)anthracene, benzo-(e)pyrene, dibenz(a,h)anthracene, triphenylene, phen-anthrene, anthracene, chrysene, benzo(c)phenanthrene, dibenzo(a,i)pyrene, dibenzo(a,h)pyrene, 7-methyl-benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, 3-methylcholanthrene, 5-methylchrysene, fluoranthene, benzo(b)fluoranthene, benzo(j)fluoranthene, benzo(k)-fluoranthene, and dibenzo(a,e)fluoranthene. 

Chrysene is a weak tumor initiator and is inactive as a complete carcinogen (38). The 1,2-dihydrodiol is more active as a mutagen than the 3,4- or the 5,6-dihydrodiols. The biological data support the hypothesis that the principal active metabolite of chrysene is the bay region anti-1,2-diol-3,4-epoxide (58). 

Chrysene was mutagenic to Salmonella typhimurium in the presence of an exogenous metabolic system. It induced sister chromatid exchanges in one mouse study and chromosomal aberrations in one hamster study. Chrysene is metabolically activated to a 1,2-diol-3,4-epoxide that is mutagenic and carcinogenic in experimental animals and forms covalent adducts with DNA. ... 

The Suzuki cross-coupling reaction is recognized as a novel, abbreviated method for the synthesis of 2-hydroxychrysene, 2-hydroxy-5-methylchrysene, and 8-hydroxy-5-methyl-chrysene from easily accessible reactants (Eq. (8)) [23]. These phenolic compounds constitute precursors for the synthesis of dihydrodiol and bay-region diol epoxide derivatives of chrysene and 5-methylchrysene, which are implicated as the active forms of carcinogenic polynuclear aromatic hydrocarbons. 

The primary toxic effect of concern for chrysene is carcinogenicity, which is most likely the result of the mutagenic activity of its metabolites, 1,2-dihydrodiol and l,2-diol-3,4-epoxide. The 1,2-dihydrodiol and the l,2-diol-3,4-epoxide have been shown to be mutagenic in vitro in bacterial and mammalian cells and have induced pulmonary adenomas when administered to newborn mice. In addition, the 1,2-dihydrodiol was active as a tumor initiating agent on mouse skin. DNA adducts in hamster cells resulting from a reaction of the DNA with l,2-diol-3,4-exp-oxide have also been detected. 

Levin W, Wood AW, Change RL, et al. 1978. Evidence for bay region activation of chrysene 1,2-dihydrodiol to an ultimate carcinogen. Cancer Res 38 1831. 

Okuda, H., Nojima, H., Watanabe, N., and Watabe, T., Sulphotransferase-mediated activation of the carcinogen 5-hydroxymethyl-chrysene. Biochem. Pharmacol. 38, 3003-3009 (1989). 

Several carcinogenic higher aromatic polycyclic hydrocarbons [are] present in tobacco smoke condensate. They include benzo[a]pyrene benzo[e]pyrene chrysene. .., benz[a] anthracene dibenz[a,/ ]anthracene and dibenzo[a,i] pyrene. .. From the amount in which these materials have been found in tobacco smoke condensate it was evident that these, by themselves, could not account for the total biological activity observed. 

Of the six purely-aromatic tetracyclic hydrocarbons, only chrysene, benz[a] anthracene and benzo[ft]phenanthrene possess even marginal activity but, as shown (Tables 4.1,4.2, and 4.3), many benz[a] anthracene derivatives are active, as are some benzo[c]phenanthrene derivatives. Substitution of one, two, or three methyl groups at 6, 7, 8, or 12 in benz[a] anthracene markedly increases activity [41]. Studies of N-mustard derivatives of anthracenes and benz[a] anthracenes [42] emphasise the parallelism between carcinogenic and carcino-static properties of poly-nuclear derivatives [43]. The marked influence of a small change in chemical structure is illustrated by the sequence of anti-tumour activities lO-ethyl-9-anthryl > 9-anthryl lO-methyl-9-anthryl for the change of meso substituent from Et to H to Me [42]. 

Polycyclic aromatic hydrocarbons (PAHs) are produced through the incomplete combustion of various materials. Air-suspended particulates adsorb PAHs so air and subsequently soil and sand will also be contantinated. PAHs generally exhibit strong carcinogenic and mutagenic activity. For example, benzo[a]pyrene (B[a]P) is known as a carcinogenic compound. Synchronously excited fluorescence spectrometry has provided a multicomponent analysis of PAHs (135). After ultrasonic extraction of PAHs, e.g., B[a]P benzo[k]fluoranthene (B[k]F), chrysene (Chry), benzo[a]anthracene (B[a]A), pyrene (Py), perylene (Pery), and benzo[ghi]petylene (B[ghi]pery), from soils, they were separated by TLC on kieselguhr G layers mixed with 26% acetylated cellulose (135). Twelve PAHs... 

Primary candidates for the mutagens (and carcinogens ) responsible for activity in the basic fractions include quinoline, substituted quinolines, alkyl pyridines, acridines, aza-arenes, naphthylamines, and aromatic amines in the neutral fractions, potential hazards may be benzanthracenes, dibenzanthracenes, substituted anthracenes, benzopyrenes, benzofluorenes, pyrene, substituted pyrenes, and chrysenes. 

The pyrolytic oils from municipal solid waste contain substantial concentration of PAH consisting mainly of naphthalene, fluorene and phenanthrene and their alkylated substituents. Some species were of known carcinogenic or mutagenic activity, e.g., methylfluorenes, phenanthrenes, chrysene, and methylchrysene. The PAH were formed via Diels Alder and deoxygenation secondary reactions. Increase in reactor temperature and residence time increased PAH concentration [382]. 

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