Synthesis and tumor-initiating activities of dimethylchrysenes

Amin, Shantu; Balanikas, George; Huie, Keith; Hecht, Stephen S.

doi:10.1021/tx00006a005

Cited by 10 publications

(25 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results were consistent with the metabolic activation pathway illustrated in Figure 1 because formation of the requisite diol epoxide was blocked in 1,5-and 5,12-diMeC but not in 5,11-diMeC (22). When we examined the tumorigenic activities of 5,6-diMeC and 5,7-diMeC, we found, to our surprise, that they were both significantly less tumorigenic than 5-MeC (8,12). 0893-228x/92/2705-0237$03.00/0 © 1992 American Chemical Society OH 5-MeC-7/7,ZS-diol-3S,4/?-epoxide Figure 1.…”

Section: Introductionsupporting

confidence: 87%

“…This pathway is illustrated in Figure 1 QS93-22~~/92/27Q5-Q237$03.QQ/Q strongest carcinogen among the six monomethylchrysenes (3-6). When we examined the tumorigenic activities of 5,GdiMeC and 5,7-diMeC, we found, to our surprise, that they were both significantly less tumorigenic than 5-MeC (8,12). The molecular shape of this diol epoxide gives it unique DNA binding and carcinogenic properties (5)(6)(7).…”

Section: Introductionmentioning

confidence: 81%

“…All starting materials were obtained from Aldrich Chemical Co., Milwaukee, WI, unless stated otherwise. 5-MeC and 5,6-diMeC were synthesized as described (8,16). The organic layer was washed with HzO, dried (MgS04), and concentrated to give 0.14 g (55%) of In a similar manner, 5,&diMeC (16) and 5,10-diMeC (18) were prepared as a mixture from the corresponding mixture of 5-(hydroxymethyl)-8-methylchrysene (12) and 5-(hydroxymethyl)-10-methylchrysene (14).…”

Section: Experimental Sectlonmentioning

confidence: 99%

“…The molecular shape of this diol epoxide gives it unique DNA binding and carcinogenic properties (5)(6)(7). In previous studies of dimethylchrysenes, we showed that 1,5-diMeC and 5,12-diMeC were inactive, but that 5,11-diMeC was highly tumorigenic (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). These results were consistent with the metabolic activation pathway illustrated in Figure 1 because formation of the requisite diol epoxide was blocked in 1,5-and 5,12-diMeC but not in 5,11-diMeC (22).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Comparative tumorigenicity of dimethylchrysenes in mouse skin

Amin¹,

Desai²,

Hecht³

1992

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

In previous studies, we have observed unexpected structure-tumorigenicity relationships among the dimethylchrysenes. Thus, 5,6-dimethylchrysene and 5,7-dimethylchrysene were only weakly tumorigenic and were significantly less active than 5-methylchrysene. These results were surprising in view of the known route of metabolic activation of 5-methylchrysene via its 1,2-diol 3,4-epoxide. In this paper, we extended our studies of structure-tumorigenicity relationships among the dimethylchrysenes. We synthesized 5,7-, 5,8-, 5,9-, and 5,10-dimethylchrysene via photochemical ring closure reactions. The tumor-initiating activities of these dimethylchrysenes on mouse skin were compared with those of 5-methylchrysene and 5,6-dimethylchrysene. 5-Methylchrysene and 5,9-dimethylchrysene were highly tumorigenic and were significantly more active than 5,6-, 5,7-, 5,8-, and 5,10-dimethylchrysene. The results of these studies, taken together with those reported in the subsequent two papers, suggest that the molecular shapes of dimethylchrysenes influence the balance between metabolic activation and detoxification pathways.

show abstract

Section: Introductionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 81%

Section: Experimental Sectlonmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparative tumorigenicity of dimethylchrysenes in mouse skin

Amin¹,

Desai²,

Hecht³

1992

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Fig. 1) were synthesized as described previously [13,17,18,19,20,211 aqueous solution and were extracted to remove unreacted tetrols [3]. The extents of DNA modification for the PAHDE-DNA were determined by nuclease Pl/prostatic acid phosphatase digestion, [T-~~PIATP post-labeling and reversed-phase HPLC analysis as described previously [22].…”

Section: Introductionmentioning

confidence: 99%

Selective Recognition of Substituted Chrysene-Diol Epoxide-2-DNA Adducts by Antiserum prepared Against DNA Adducts of Benzo[c]Phenanthrene-Diol Epoxide-2

Einolf

Gross

Butch

et al. 1997

Polycyclic Aromatic Compounds

Self Cite

View full text Add to dashboard Cite

Polyclonal antiserum prepared against DNA that was modified with racemic benzo[c]phenanthrene-3,4-diol-1,2-epoxide-2 (B[c]PhDE-2; benzylic hydroxyl and epoxide oxygen trans) was characterized for specificity of antigen recognition. Previous studies have demonstrated that the antisera stereoselectively recognized B[c]PhDE-2-DNA and failed to recognize DNA modified with racemic benzo[c]phenanthrene-3,4-diol-1,2-epoxide-l (B[c]PhDE-I-DNA, benzylic hydroxyl and epoxide oxygen cis), benzo[a]pyrene-7,8-diol-9,lO-epoxide-2-DNA (B[a]PDE-2-DNA) and 7,12-dimethylbenz-[a]anthracene-3,4-diol-l,2-epoxide-l-DNA (DMBADE-I -DNA). DNA samples modified by diol-epoxide-2 diastereomers of several hydrocarbons were tested in competitive ELISA assays utilizing B[c]PhDE-2-DNA (270 fmol adducts per well). DNA modified with racemic diol-epoxide-2 of various substituted chrysenes (including chrysene, benzok]chrysene (Bk]C), 6-methylchrysene (6-MeC), and 5-methychrysene (5-MeC), gave 50% inhibition of antisera binding at significantly higher concentrations (5 to 7-fold) than the parent B[c]PhDE-2-DNA or 5,6-diMeCDE-DNA. DNA modified with 5,7-dimethylchryseneDE-2 (5,7-diMeCDE-2) and dibenzo[a,l]pyreneDE-2 (DB[a,d PDE-2) required 20 and > 100-fold greater levels of adducts to give 50% inhibition. Results with B[c]Ph, 5,6-diMeC, chrysene, 6-MeC and 5-MeC diol epoxide-2-DNA indicate that substitution of a methyl group in the vicinity of the bay-region of the PAHmolecule had limited effects on antigen recognition by this antiserum. However. the addition of a ring or methyl group remote from the diol epoxide moiety, as in DB[tr.l] PDE-2-DNA or 5,7-diMeCDE-?-DNA greatly decreased antigen recognition. The ability of this antiserum to recognize DNA adducts of a particular class of polycyclic aromatic hydrocarbons will be useful for studies of their contribution to the DNAbinding that results from exposure to complex environmental mixtures.

show abstract

Synthesis, Structural, and Photophysical Properties of the First Member of the Class of Pyrene‐Based [4]Helicenes

Feng

Paudel

et al. 2013

Eur J Org Chem

View full text Add to dashboard Cite

A convenient route to a new class of pyrene‐based [4]helicenes is presented. Wittig reaction of 7‐tert‐butyl‐1,3‐dimethyl‐5‐formylpyrene with benzyltriphenylphosphonium salts in the presence of nBuLi afforded 7‐tert‐butyl‐1,3‐dimethyl‐5‐(phenylethenyl)pyrenes, from which 4,5‐naphthalene annulated aromatic [4]helicenes, namely 7‐tert‐butyl‐1,3‐dimethyl‐13‐methoxydibenzo[ij,no]tetraphene and 7‐tert‐butyl‐1,3,12,14‐tetramethyldibenzo[ij,no]tetraphene, were obtained by photoinduced intramolecular cyclization. The chemical structures of these [4]helicenes were determined on the basis of their elemental analyses and spectroscopic data. The helicity in the synthesized [4]helicene induced by the presence of the second methyl group in the fjord region is discussed in detail. The photophysical and electrochemical properties of these newly developed [4]helicenes were fully investigated by UV/Vis absorption and photoluminescence spectrphotometry, and cyclic voltammetry (CV), and the crystal structures were determined for two examples.

show abstract

Synthesis and tumor-initiating activities of dimethylchrysenes

Cited by 10 publications

References 14 publications

Comparative tumorigenicity of dimethylchrysenes in mouse skin

Comparative tumorigenicity of dimethylchrysenes in mouse skin

Selective Recognition of Substituted Chrysene-Diol Epoxide-2-DNA Adducts by Antiserum prepared Against DNA Adducts of Benzo[c]Phenanthrene-Diol Epoxide-2

Synthesis, Structural, and Photophysical Properties of the First Member of the Class of Pyrene‐Based [4]Helicenes

Contact Info

Product

Resources

About