Characterization of a photoproduct of 7,12-dimethylbenz[<i>a</i>]anthracene and its effects on chick-embryo cells in culture

Warshawsky, David; Kerns, Edward H.; Bissell, Mina J.; Calvin, Marie-Claude

doi:10.1042/bj1640481

Cited by 14 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…developed in benzene (Warshawsky et al, 1977). The UV spectra and chromatographic properties of this compound were found to be identical to those reported for DMBA-endoperoxide (Warshawsky et at., 1977).…”

Section: Radiochemicalssupporting

confidence: 79%

“…The initial photo-oxidation product of DMBA has been identified as 7,12-epidioxy-7,12dimethylbenz(a)anthracene (DMBA-endoperoxide) (Cook et al, 1939;Cook and Martin, 1940;Sandin and Fieser, 1940). DMBA photo-oxidation products have lower carcinogenic activity than DMBA (Badger et al, 1940;Davies et al, 1972;Urbach et al, 1976), but the endoperoxide was found to be more toxic than DMBA to secondary cultures of chick fibroblasts (Warshawsky et al, 1977).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effect of light on the hydrocarbon‐DNA adducts formed in hamster embryo cells

Baird

1978

Intl Journal of Cancer

View full text Add to dashboard Cite

Polycyclic aromatic hydrocarbons are metabolically activated and bind to DNA in hamster embryo cell cultures. The effect of light exposure on the DNA adducts formed from two hydrocarbons of different photosensitivities was investigated by exposing cells to light during hydrocarbon treatment and by exposing DNA to light after isolation from cells treated with hydrocarbon in darkness. The total hydrocarbon‐DNA adducts formed per mg DNA in cells treated with the highly photosensitive hydrocarbon 7,12‐dimethylbenz(a)anthracene (DMBA) in the presence of light was less than in cells treated in darkness. No appreciable amounts of hydrocarbon‐DNA adducts were formed in cells treated with a major photo‐oxidation product of DMBA, the 7,12‐endoperoxide, in either the presence or absence of light. DMBA‐deoxyribonucleoside adducts were analyzed by chromatography on Sephadex LH20 columns. Exposure to light of the DMBA‐deoxyribonucleoside adducts obtained by enzymatic degradation of DNA isolated from cells treated with DMBA in darkness converted more than half to photoproducts. DNA that was exposed to light prior to degradation contained less than half as many photoproducts and had an elution profile similar to that obtained from DNA isolated from cells treated with DMBA in the presence of light. With the less photosensitive hydrocarbon benzo(a)pyrene, benzo(a)pyrene‐DNA adducts were identical for DNA from cells treated with benzo(a)pyrene in darkness, DNA from cells treated in the presence of light, and DNA exposed to light after isolation. These results indicate that exposure to light does not alter the mechanism of binding of hydrocarbons to DNA in hamster embryo cells, but does affect the DNA adducts of the photosensitive hydrocarbon DMBA in a similar manner in cells and in isolated DNA.

show abstract

Section: Radiochemicalssupporting

confidence: 79%

mentioning

confidence: 99%

Effect of light on the hydrocarbon‐DNA adducts formed in hamster embryo cells

Baird

1978

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…However, 7-hydroxymethyl-12-methylbenz[a]anthracene has been shown to cause adrenal apoplexy and mammary cancer in rats (2) and so is not considered a detoxification intermediate. 7,12-Epidioxy-7,12-dimethylbenz[a]anthracene, a photooxidation product of DMBA (35), has been shown to be toxic to chicken fibroblast cells (34). While mass spectrometric analysis showed no 7,12-epidioxy-7,12-dimethylbenz[a]anthracene present in the DMBA used in treating the Mycobacterium cells, the compound did form in the control flask.…”

Section: Discussionmentioning

confidence: 92%

Regio- and Stereoselective Metabolism of 7,12-Dimethylbenz[ a ]anthracene by Mycobacterium vanbaalenii PYR-1

Moody

Freeman

et al. 2003

Appl Environ Microbiol

View full text Add to dashboard Cite

The degradation of 7,12-dimethylbenz[a]anthracene (DMBA), a carcinogenic polycyclic aromatic hydrocarbon, by cultures of Mycobacterium vanbaalenii PYR-1 was studied. When M. vanbaalenii PYR-1 was grown in the presence of DMBA for 136 h, high-pressure liquid chromatography (HPLC) analysis showed the presence of four ethyl acetate-extractable compounds and unutilized substrate. Characterization of the metabolites by mass and nuclear magnetic resonance spectrometry indicated initial attack at the C-5 and C-6 positions and on the methyl group attached to C-7 of DMBA. The metabolites were identified as cis-5,6-dihydro-5,6-dihydroxy-7,12-dimethylbenz[a]anthracene (DMBA cis-5,6-dihydrodiol), trans-5,6-dihydro-5,6-dihydroxy-7,12-dimethylbenz[a]anthracene (DMBA trans-5,6-dihydrodiol), and 7-hydroxymethyl-12-methylbenz[a]anthracene, suggesting dioxygenation and monooxygenation reactions. Chiral stationary-phase HPLC analysis of the dihydrodiols showed that DMBA cis-5,6-dihydrodiol had 95% 5S,6R and 5% 5R,6S absolute stereochemistry. On the other hand, the DMBA trans-5,6-dihydrodiol was a 100% 5S,6S enantiomer. A minor photooxidation product, 7,12-epidioxy-7,12-dimethylbenz[a]anthracene, was also formed. The results demonstrate that M. vanbaalenii PYR-1 is highly regio-and stereoselective in the degradation of DMBA.7,12-Dimethylbenz[a]anthracene (DMBA) is a potent carcinogen in rodent skin and mammary cells (7). Alkylated benz[a]-anthracenes are formed in sediments by thermal processes and have also been identified in cigarette smoke condensate, coal gasification and stock gas particulates, and roofing tar extracts (1, 10). Studies from several laboratories have indicated that DMBA is bioactivated by various isoforms of mammalian cytochrome P-450 and epoxide hydrolase to form DMBA-3,4-dihydrodiol-syn-and anti-1,2-epoxides that react with DNA to form adducts that lead to tumor initiation (22,32,33). An alternative mechanism for metabolic activation is hydroxylation of the alkyl side chain to form hydroxymethyl derivatives, followed by sulfotransferase-catalyzed activation of DMBA to form electrophilic sulfuric acid esters that bind to DNA (6). 7,12-Dimethylbenz[a]anthracene has been used as a model polycyclic aromatic hydrocarbon (PAH) in the following ways: (i) as a tumor initiator or as a complete carcinogen in rodent skin and mammary gland models of carcinogenesis (15, 22), (ii) as a prototype methyl-substituted PAH in mutation and cancer research (15), (iii) to determine whether metabolic activation occurs via bay-region dihydrodiol epoxide metabolites or hydroxylation of the methyl substituent with subsequent formation of electrophilic sulfuric acid esters (6), and (iv) to determine the environmental fate of methyl-substituted PAHs.In contrast to the numerous studies of the metabolism, DNA adduct formation, and tumor induction by DMBA in mammalian cells, little is known about the microbial metabolism of this potent carcinogen. Several strains of fungi metabolize methylbenz [a]anthracenes at the methyl group, with furth...

show abstract