Fluoranthenes carcinogenic activity

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. 

Fluoranthene is one of the more prevalent PAH in the human environment. Although fluoranthene is not active as a carcinogen, its 2- and 3-methyl derivatives have been shown to be active as tumor initiators (105). The major mutagenic metabolite of fluoranthene in the Ames assay has been identified as the 2,3-dihydrodiol (31)... 

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... 

Although the PAHs are similar, they have structural differences that are the basis for differences in metabolism and relative carcinogenicity. The metabolism of the more carcinogenic, alternant (equally distributed electron density) PAHs, such as benzo(a)pyrene, benzo(a)anthracene, and dibenz(a,h)anthracene, seems to differ in some ways from that of nonalternant (imeven electron density distribution) PAHs, such as fluoranthene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(j)fluoranthene, and indeno(l,2,3-cd)pyrene [31]. As can be seen, most of the studies on the metabolic pathways of PAHs have been done on rodent, therefore little is known on the metabolism of these compounds in nonrodent species. Due to specie differences there may be some slight differences in the enzymes that activate PAHs and in the formation of DNA adducts. 

This structure-activity relationship has been supported by several findings. According to Iball index which is proportional to the fraction of subject animal that shows a carcinogenic response divided by the mean latent period, dibezo(a,l)pyrene has the maximum value of 74, benzo(a)pyrene has 72, other compounds with a bay region in their structures have values above 50 while compounds such as fluoranthene, tiiphenylene, and phenanthrene without any bay or fjord region have a value of 0 [11]. 

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