Disease relevance of HSDB 6979

• Each of the remaining PAH induced both adenomas and DNA adducts in a dose-dependent manner, with dibenz[a,h]anthracene > 5-methylchrysene > cyclopenta[c,d]pyrene > benzo[a]pyrene > benzo[b]fluoranthene [1].
• The metabolic activation of the environmental carcinogen 5-methylchrysene was studied by combining high-pressure liquid chromatographic analysis of metabolites formed in vitro with assays of these metabolites for mutagenic activity toward Salmonella typhimurium [2].
• Cultures of a human mammary carcinoma cell line (MCF-7) were exposed to the soluble organic fraction of diesel particle emissions, benzo[a]pyrene (B[a]P) and 5-methylchrysene (5-MeCHR) to study time- and dose-related PAH-DNA binding [3].

High impact information on HSDB 6979

• We compared the metabolism of the tobacco smoke constituents 5-methylchrysene (5-MeC), a strong carcinogen, and 6-MeC, a weak carcinogen, in 18 hepatic and 11 pulmonary human microsomes [4].
• Rates of hydrolysis and extents of DNA binding of 5-methylchrysene dihydrodiol epoxides [5].
• 5-Methylchrysene is metabolically converted to the bay-region dihydrodiol-epoxides, trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (DE-I), in which the methyl group and the epoxide ring are in the same bay region, and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene (DE-II) [6].
• Influence of bay-region methyl group on formation of 5-methylchrysene dihydrodiol epoxide:DNA adducts in mouse skin [7].
• The three-dimensional structure of the product of the reaction of a diol epoxide of the carcinogen 5-methylchrysene with methanol has been determined by an X-ray diffraction analysis [8].

Chemical compound and disease context of HSDB 6979

• The induction of DNA adducts and adenomas in the lungs of strain A/J mice has been investigated following the single i.p. administration of each of the following polycyclic aromatic hydrocarbons (PAH): pyrene, dibenz[a,h]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, 5-methylchrysene, and cyclopenta[c,d]pyrene [1].

Biological context of HSDB 6979

• For identification of these products, markers were prepared from 5-methylchrysene bay-region dihydrodiol epoxides [7].
• An SV40-based pS189 shuttle vector, which contained a supF target gene and was replicated in human cells (Ad293), was used to determine the mutational specificity of anti 5-methylchrysene 1,2-dihydrodiol 3,4-epoxide, the active metabolite of the environmentally prevalent carcinogen 5-methylchrysene [9].
• Of 23 PAHs examined, benz[a]anthracene (B[a]A), benzo[b]fluoranthene, and 5-methylchrysene were the most potent inhibitors of P450 1A2- and 1B1-catalyzed EROD activity, with IC50 values <10 nM [10].

Associations of HSDB 6979 with other chemical compounds

• The metabolic activation in mouse skin of the strong carcinogen, 5-methylchrysene (5-MeC) was compared to that of the inactive compound, 6-nitro-5-methylchrysene (6-NO2-5-MeC) [11].
• It is shown that more in-plane distortions are found for 5-methylchrysene derivatives than for methylbenz[a]anthracene derivatives and this, it is suggested, results from the nature of the flexibility of the chrysene compared with the benz[a]anthracene fragment at the bay-region [12].
• The two pairs of diastereomeric anti- and syn-diolepoxide derivatives of 5-methylchrysene in both bay regions were tested for cytotoxicity and for mutagenicity at the hprt locus of chinese hamster V79 cells as determined by the ability of the cells to form colonies in medium containing 6-thioguanine [13].
• Although microM concentrations of PAHs were required to reach the inhibition level equal to the model tumor promoter phorbol 12-myristate 13-acetate (IC50 = 8 nM), 12 of the PAHs under study were found to be strong inhibitors of GJIC (strongest effects were observed with fluoranthene, picene, 5-methylchrysene and nine additional PAHs) [14].

Gene context of HSDB 6979

• The present findings indicate that the higher carcinogenic potency of 5-methylchrysene cannot be related to its mutagenic potential or its ability to enhance its own activation through induction of CYP1A1 and epoxide hydrolase activities [15].
• Tumor multiplicity, DNA adducts and K-ras mutation pattern of 5-methylchrysene in strain A/J mouse lung [16].
• In addition, we found that three selected PAHs (5-methylchrysene, B[a]P, and B[a]A) inhibited metabolic activation of 5-methylchrysene-1,2-diol, (+/-)-B[a]P-7,8-diol, dibenzo[a,l]pyrene-11,12-diol, and MeIQ to genotoxic metabolites catalyzed by P450s 1A1, 1B1, and 1A2, respectively, in S. typhimurium NM2009 [10].

Analytical, diagnostic and therapeutic context of HSDB 6979

• Northern blot analysis revealed a decrease in the expression of jun transcripts 24 h following the exposure of Clara cells to the direct acting forms of benzo[a]pyrene (BPDE*) or 5-methylchrysene (5MeCDE) [17].

References