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F B Daniel

Publications and source records attributed to F B Daniel.

At least 55 records · Page 3Linked to original sources
PubMed1989

The further development of a mammalian DNA alkaline unwinding bioassay with potential application to hazard identification for contaminants from environmental samples.

Recently, we have detailed a DNA alkaline unwinding assay (DAUA) that can be used to rapidly measure chemically induced strand breaks in mammalian cells (Daniel et al., 1985). In this paper we present further development of this assay, including: (1) studies on the relationship between DNA adducts and DNA strand breaks; (2) evaluation of the role of cytotoxicity in DNA strand breaks; and (3) application of the DAUA to cell preparations from the liver of mice dosed with methylating agents. The level of DNA adducts produced in human CCRF-CEM cells by treatment with benzo(a)pyrene diol-epoxide (BPDE), N-acetoxy-2-acetyl aminofluorene (AAAF), and various methylating agents was linear with concentration over several orders of magnitude. Likewise, the level of strand breaks increased with the concentration over the same dose range. The strand breaks/adduct ratio ranged from 0.05 for the methyl adducts to 0.001 for the BPDE adducts. Using these values and the inherent sensitivity of the DAUA (circa 100 to 1000 breaks/cell), (Daniel et al., 1985), the ability of the assay to detect DNA damage induced by various classes of chemical carcinogens can be calculated. The DAUA appears to be useful for assessing the relative potency of various environmental genotoxic effects on mammalian cells. In addition, it can be conducted on cells isolated from target organs of whole animals.

Animals↗
PubMed1989

Chloroform inhibition of 1,2-dimethylhydrazine-induced gastrointestinal tract tumors in the Fisher 344 rat.

The effect of chloroform (CHCl3), administered at 0, 900, and 1800 mg/liter in the drinking water, on the carcinogenic potency of 1,2-dimethylhydrazine (DMH) was investigated. Groups of 40 male Fisher 344 rats were given one of the three drinking water solutions for 39 weeks following the subcutaneous injection of 200 mg/kg DMH, a known gastrointestinal (GI) tract carcinogen in this animal strain. When tumors from the GI tract were pooled there was a highly significant (p less than 0.001) decrease in total number of tumors per group with increasing concentration of drinking water CHCl3. In the control group (0 mg/liter CHCl3), 14/39 (36%) of the animals developed tumors of the GI tract, including the duodenum, jejunum, stomach, cecum, and colon. In contrast, the incidence of tumors in the two groups of rats given CHCl3 in the drinking water was significantly lower (p less than 0.001; 900 mg/liter CHCl3, 12.8%; 1800 mg/liter CHCl3, 12.5%). A similar relationship was obtained when colon tumors were analyzed independently (p = 0.01). The incidence of total colon tumors obtained in the control group of this study (10/39, 26%) agrees well with the previous study by B.S. Reddy, K. Watanabe, and J.H. Weisburger (1977, Cancer Res. 37, 4156-4159) conducted in the same rat strain (7/30, 23%). These results demonstrate that CHCl3 in the drinking water inhibits carcinogenesis in the rat GI tract.

1,2-Dimethylhydrazine↗
PubMed1988

Metabolism of bis(2-methoxyethyl) ether in the adult male rat: evaluation of the principal metabolite as a testicular toxicant.

The metabolism of the reproductive toxicant bis(2-methoxyethyl) ether was studied in male Sprague-Dawley rats, and the principal metabolite (2-methoxyethoxy)acetic acid and its metabolic precursor 2-(2-methoxyethoxy)ethanol were evaluated separately as testicular toxicants. For the metabolism study, rats were given single po doses of [1,2-ethylene-14C]bis(2-methoxyethyl) ether at 5.1 or 0.051 mmol/kg body wt. Within 96 hr, approximately 86 to 90% of the radioactivity was excreted in the urine. Urinary metabolites were separated by high-performance liquid chromatography and isolated for characterization by gas chromatography-mass spectrometry. The principal urinary metabolite, accounting for 67.9 +/- 3.3% of the administered high dose and 70.3 +/- 1.3% of the low dose, was identified as (2-methoxyethoxy)acetic acid. A second metabolite, representing 6.2 +/- 0.8% of the high dose and 5.8 +/- 0.8% of the low dose, was identified as methoxyacetic acid, a previously recognized testicular toxicant. In the toxicity study, (2-methoxyethoxy)acetic acid and 2-(2-methoxyethoxy)ethanol were administered to rats at 5.1 mmol/kg body wt by gavage as single daily doses for as many as 20 consecutive days. The testes of rats killed 24 hr after the administration of even numbered doses showed no gross or microscopic abnormalities. These results are in contrast to the previously reported testicular atrophy evoked after as few as 8 daily doses of the parent compound, bis(2-methoxyethyl) ether, tested under the same experimental conditions. Thus, the testicular toxicity reported for bis(2-methoxyethyl) ether could be explained by the presence of a minor metabolite, methoxyacetic acid.

Acetates↗
PubMed1986

Genotoxic properties of haloacetonitriles: drinking water by-products of chlorine disinfection.

Chlorinated and brominated haloacetonitriles (HAN), known drinking water contaminants which form during chlorine disinfection, were investigated for genotoxic activity. The HAN produced DNA strand breaks in cultured human lymphoblastic (CCRF-CEM) cells, bound to the nucleophilic trapping agent 4-(p-nitrobenzyl)pyridine and formed a covalent bond to polyadenylic acid in a cell-free reaction system. Thus, we have demonstrated that these chemicals are genotoxic, which would indicate a potential for carcinogenic activity and for human health hazard.

Acetonitriles↗
PubMed1986

A comparison of covalent DNA binding of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in respiratory tissues from human, rat and mouse.

In vivo and in vitro covalent DNA binding was investigated in an attempt to explain the higher susceptibility of A/J mouse lung and Fischer-344 rat trachea to 7,12-dimethylbenz[a]anthracene (DMBA) as compared to benzo[a]pyrene (BP), and to evaluate the relative susceptibility of the human respiratory tract to these compounds. After in vivo administration of either BP or DMBA to A/J mice covalent DNA binding was higher in the liver than in the lungs. Forty-eight hours after administration, but not before, binding of DMBA was higher than that of BP in both organs. In vitro studies using cultured explants of both human and A/J mouse peripheral lung, as well as human bronchus and Fischer-344 rat trachea, revealed that covalent DNA binding of DMBA to mouse lung and rat trachea were similar and that both were significantly higher than that of BP to these organs. Binding of BP and DMBA was similar in both human tissues and did not differ from BP binding in the animal tissues. Enzymatic hydrolysis and HPLC separation of the DNA-hydrocarbon adducts revealed that patterns of adducts in human and mouse peripheral lung were similar and qualitatively resembled known patterns in other target and non-target tissues. It is concluded that the higher susceptibility of the mouse lung and rat trachea to DMBA as compared to BP may be related to the higher covalent DNA binding of the former and that the relative carcinogenic risk of the human respiratory tract after exposure to DMBA may be the same as that after BP exposure.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Haloacetonitriles: metabolism, genotoxicity, and tumor-initiating activity.

Haloacetonitriles (HAN) are drinking water contaminants produced during chlorine disinfection. This paper evaluates metabolism, genotoxicity, and tumor-initiating activity of these chemicals. The alkylating potential of the HAN to react with the electrophile-trapping agent, 4-(p-nitrobenzyl)pyridine, followed the order dibromoacetonitrile (DBAN) greater than bromochloroacetonitrile (BCAN) greater than chloroacetonitrile (CAN) greater than dichloroacetonitrile (DCAN) greater than trichloroacetonitrile (TCAN). When administered orally to rats, the HAN were metabolized to cyanide and excreted in the urine as thiocyanate. The extent of thiocyanate excretion was CAN greater than BCAN greater than DCAN greater than DBAN much greater than TCAN. Haloacetonitriles inhibited in vitro microsomal dimethylnitrosamine demethylase (DMN-DM) activity. The most potent inhibitors were DBAN and BCAN, with Ki = 3-4 X 10(-5) M; the next potent were DCAN and TCAN, with Ki = 2 X 10(-4) M; and the least potent inhibitor was CAN, with Ki = 9 X 10(-2) M. When administered orally, TCAN, but not DBAN, inhibited hepatic DMN-DM activity. The HAN produced DNA strand breaks in cultured human lymphoblastic (CCRF-CEM) cells. TCAN was the most potent DNA strand breaker, and BCAN greater than DBAN greater than DCAN greater than CAN, which was only marginally active. DCAN reacted with polyadenylic acid and DNA to form adducts in a cell-free system; however, the oral administration of DBAN or DCAN to rats did not result in detectable adduct formation in liver DNA. None of the HAN initiated gamma-glutamyltranspeptidase (GGT) foci when assayed for tumor-initiating activity in rat liver foci bioassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetonitriles↗
PubMed1985

Quantitation of chemically induced DNA strand breaks in human cells via an alkaline unwinding assay.

DNA strand breaks induced in human CCRF-CEM cells by electrophilic chemicals (carcinogens/mutagens) can be readily quantitated via a facile alkaline unwinding assay. This procedure estimates the number of chemically induced DNA strand breaks on the basis of the percentage DNA converted from double-stranded to single-stranded form during an exposure to the alkaline unwinding conditions. The assay is based on the assumption that each strand break serves as a strand unwinding point during the alkaline denaturation. The extent of strand separation can be standardized with respect to the initial level of induced strand breaks by the use of X-rays, which produce known levels of DNA strand breaks per rad in mammalian cells. Subsequent to the alkaline exposure, the single- and double-stranded DNA were separated by use of thermostated hydroxylapatite columns (60 degrees C), and the DNA was quantitated via a fluorescence assay (Hoechst 33258 compound). A correlation was shown between mammalian DNA strand-breaking potential (as measured in this procedure) and the propensity of these chemicals to revert Salmonella typhimurium TA100.

Cells, Cultured↗
PubMed1985

Effects of selenium on 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis and DNA adduct formation.

The purpose of the present investigation was to determine the effects of dietary selenium deficiency or excess on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary neoplasia in rats and to delineate whether selenium-mediated modification of mammary carcinogenesis was associated with changes in carcinogen:DNA adduct formation and activities of liver microsomal enzymes that are involved in xenobiotic metabolism. Female Sprague-Dawley rats were divided into three groups from weaning and were maintained on one of three synthetic diets designated as follows: selenium deficient (less than 0.02 ppm); selenium adequate (0.2 ppm); or selenium excess (2.5 ppm). For the DMBA binding and DNA adduct studies, rats were given a dose of [3H]DMBA p.o. after 1 month on their respective diets. Results from the liver and the mammary gland indicated that neither selenium deficiency nor excess had any significant effect on the binding levels, which were calculated on the basis of total radioactivity isolated with the purified DNA. Furthermore, it was found that dietary selenium intake did not seem to affect quantitatively or qualitatively the formation of DMBA:DNA adducts in the liver. Similarly, in a parallel group of rats that did not receive DMBA, the activities of aniline hydroxylase, aminopyrine N-demethylase, and cytochrome c reductase were not significantly altered by dietary selenium levels. Concurrent with the above experiments, the effect of dietary selenium intake on carcinogenesis was also monitored. Results of this experiment indicated that selenium deficiency enhanced mammary carcinogenesis only when this nutritional condition was maintained in the postinitiation phase. Likewise, an excess of selenium intake inhibited neoplastic development only when this regimen was continued after DMBA administration. In either case, deficient or excess selenium at the time of carcinogenic insult failed to produce a significant effect on subsequent tumor yield, if selenium intake was returned to normal during the proliferative phase of tumor growth. Based on the results of these studies, it is suggested that selenium-mediated modification of mammary tumorigenesis is not exerted via alterations in carcinogenic initiation (i.e., metabolism or DNA adduct formation).

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Inhibition of benzo(a)pyrene and benzo(a)pyrene-trans-7,8-diol metabolism and DNA binding in mouse lung explants by ellagic acid.

The effect of ellagic acid, a naturally occurring plant phenol, on the binding to DNA and metabolism of benzo(a)pyrene (BP) and trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene (BP 7,8-DHD) in cultured explants of strain A mouse lung was investigated. The explants were cultured in a rocking organ culture chamber for 16 h in the presence or absence of 10, 25, 50, and 100 microM ellagic acid. These concentrations of ellagic acid were nontoxic as determined by biochemical and histological methods. The ellagic acid was then removed from the cultures, and the explants were incubated with either 1 microM [3H]BP or [3H]BP 7,8-DHD for 24 h. Explant DNA was isolated using hydroxylapatite chromatography, and the BP metabolites in the medium were analyzed by high-pressure liquid chromatography. Ellagic acid (50 microM) inhibited the binding of BP and BP 7,8-DHD to lung DNA by 46 to 50% and 60 to 70%, respectively. High-pressure liquid chromatography analysis showed that ellagic acid (100 microM) inhibited the metabolism of BP by 20 to 40% and of BP 7,8-DHD by 20%, as indicated by the increased amounts of unmetabolized substrates and decreased amounts of metabolites in the medium. The major BP:DNA adduct in the explants was 7R-N2-[10 beta-[7 beta, 8 beta, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]yl: deoxyguanosine, and its formation was reduced by 60 to 65% in the presence of 100 microM ellagic acid. These data suggest that the reduction of BP and BP 7,8-DHD metabolite binding to DNA by ellagic acid may have been due to inhibition of the formation and/or removal of BP 7,8-diol-9,10-epoxide prior to its binding to DNA.

Animals↗
PubMed1984

Metabolism and DNA adduct formation of 2-acetylaminofluorene by bladder explants from human, dog, monkey, hamster and rat.

Cultured bladder explants from human, dog, monkey, hamster and rat were used to study the metabolism, and DNA-adduct formation of [3H]2-acetylaminofluorene (AAF). After 24 h of incubation with 1 microM [3H]AAF, the organic-soluble and glucuronide fractions represented 29.0-58.4% and 0.7-10.8%, respectively, of the total amount of radioactive material in the medium. In the organic-soluble fraction of all species, the presence of both ring-hydroxylated (at the 7-, 9-, 5-, 3- and 1-carbons) metabolites and N-hydroxy-AAF could be demonstrated, with 7-hydroxy-AAF and 9-hydroxy-AAF being the most ubiquitous metabolic products. In addition, 2-aminofluorene could be detected in all cases with the highest amounts formed by dog bladder explants. Species susceptible to aromatic amine-induced bladder carcinogenesis (human and dog) showed widely varying DNA binding (0.23 +/- 0.20 and 1.95 +/- 1.2 mumol AAF/mol deoxyribonucleotide, respectively), and in explants of the less susceptible species (monkey, hamster and rat) DNA binding was comparable (0.46 +/- 0.21, 0.37 +/- 0.07 and 0.34 +/- 0.27, respectively). Enzymatic hydrolysis of the [3H]AAF--DNA to the nucleoside level revealed that N-(deoxyguanosine-8-yl)-2-aminofluorene, together with small amounts (5.9-15.4% of the total) of its imidazole ring-opened derivative, was the most ubiquitous adduct formed (17.8-47.2% of the total) in all species, except the dog. In dog bladder DNA, N-(deoxyguanosine-8-yl)-2-acetylaminofluorene was the principal DNA adduct (39.0-46.5% of the total) with smaller amounts (15.5-22.2% of the total) in the other species. In addition, small amounts (3.5-8.6% of the total) of another adduct, 3-(deoxygaunosin-N2-yl)-2-acetylaminofluorene, could be detected in all cases. It is concluded that bladder explants of the human, dog, monkey, hamster and rat metabolize AAF mainly to ring-hydroxylated products, but also form small amounts of the proximate carcinogenic metabolite N-hydroxy-AAF. Neither the overall binding of AAF to bladder DNA, nor the formation of specific AAF--DNA adducts is correlated with the relative susceptibilities of these five species to aromatic amine-induced urinary bladder carcinogenesis.

2-Acetylaminofluorene↗
PubMed1984

7,12-Dimethylbenz[a]anthracene--DNA adducts in Sprague-Dawley and Long-Evans female rats: the relationship of DNA adducts to mammary cancer.

7,12-Dimethylbenz[a]anthracene (DMBA) is a powerful carcinogen to the mammary gland of the pubescent female Sprague-Dawley (S.D.) rat but is a much less potent inducer of mammary adenocarcinoma in the female Long-Evans (L.E.) rat of the same age. The livers of both strains are refractory to DMBA. The maximum levels of DMBA--DNA adducts formed, in both the mammary gland and liver following i.p. administration of [3H]DMBA (21 mumol) were significantly higher (p less than 0.01) in the resistant L.E. strain than the sensitive S.D. strain. Maximal levels of DMBA--DNA adducts were observed at approximately 48 h post administration of the hydrocarbon for both organs of both strains. For the S.D. animals no significant loss of adducts (relative to the 48 h maxima) was observed from either organ at the last time point (336 h). In contrast both organs of the L.E. strain showed some evidence of adduct removal. Analysis of the DMBA--deoxyribonucleoside adducts by h.p.l.c. following enzymatic hydrolysis of the purified DNA showed that A-ring diol-epoxide adducts of both DMBA and a major metabolite 7-hydroxymethyl-12-methylbenz[a]anthracene (7OHM-12MBA) were present in both organs from both strains. In both strains the levels of 7OHM-12MBA adducts were less, relative to the DMBA adducts, in the mammary gland than in the liver. With respect to specific adduct removal, L.E. animals removed approximately 70% of the identifiable adducts from the liver DNA in the 48 h to 336 h (12 d) time period. In contrast the S.D. animals showed no such capability for removing these adducts during this same time frame. These observations indicate that some factor(s) in addition to, or in conjunction with, the levels of DMBA--DNA adducts initially formed are responsible for the overall relative sensitivities of the S.D. and L.E. mammary gland to this hydrocarbon. One such parameter might be the relative propensity for specific adduct removal or the relative capacity of the two strains to repair DMBA-induced DNA damage.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Comparative metabolism of 7,12-dimethylbenz[a]-anthracene and its non-carcinogenic 2-fluoro analogue by Syrian hamster embryo cells.

The metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) and its non-carcinogenic 2-fluoro analogue (2F-DMBA) by Syrian hamster embyro (SHE) cells has been studied using high pressure liquid chromatography (HPLC) and fluorescence spectroscopy. Metabolites produced by SHE cells were compared chromatographically to those produced on a larger scale by liver microsomal preparations and previously identified by gas chromatography and mass spectrometry. At least 2 (possibly 3) phenol metabolites, none of which appear to be in the A-ring, were formed from [3H] 2F-DMBA and totalled only 3% of the organic extractable activity present in the media at 24 h. On the other hand, 3 A-ring phenols (DMBA-2-ol, DMBA-3-ol and DMBA-4-ol) comprising almost 12% of the total organic extractable radioactivity at 24 h were identified as metabolites in SHE cell culture media. For both hydrocarbons the major organic extractable metabolite present at 24 h was the respective 8,9-dihydro-dihydroxydiol (DMBA 45%, 2F-DMBA 39%). Thus, substitution of fluorine for hydrogen at the 2-carbon of DMBA appears to block or greatly reduce the A-ring metabolism of this compound but has relatively little effect on D-ring oxidation. Therefore loss of the carcinogenic/mutagenic activity of DMBA correlates with the extent of A-ring metabolism including, possibly, the bay region diol epoxide.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Interactions of chrysotile and benzopyrene in a human cell culture systems.

The risk of lung cancer related to asbestos exposure has been shown to increase disproportionately by cigarette smoking, suggesting a synergistic effect. Differing lengths of NIEHS chrysotile with benzopyrene [B(a)P, B(e)P] (organic by-products of combustion) were applied on normal human fibroblasts (cell line CI) to test for cytotoxicity (survival determined by colony-forming efficiency), binding of benzopyrene to DNA, and the production of benzopyrene metabolites. At concentrations of 100 micrograms/mL, NIEHS short chrysotile was more cytotoxic than NIEHS intermediate chrysotile (3% and 17% survival, respectively); B(a)P and B(e)P concentrations up to and including 10 microM were not cytotoxic. Simultaneous application of NIEHS short chrysotile with B(a)P or B(e)P did not decrease survival synergistically. On the contrary, application of B(a)P simultaneously with NIEHS intermediate chrysotile resulted in increased survival over that of intermediate chrysotile alone (25% and 17% survival, respectively). There were low levels of B(a)P bound to DNA in the presence of NIEHS short chrysotile or NIEHS intermediate chrysotile. Measurable levels of B(a)P-DNA adducts were formed both in the absence and in the presence of each size of NIEHS chrysotile. However, there was no strong indication of a perturbation of the level of DNA-B(a)P binding following simultaneous administration of increasing levels of asbestos in addition to 1 microM hydrocarbon. The asbestos had no demonstrable influence on the level of B(a)P metabolism during the 24-hr period following simultaneous exposure of asbestos and hyrdocarbons.(ABSTRACT TRUNCATED AT 250 WORDS)

Asbestos↗
PubMed1983

In vitro assessment of asbestos genotoxicity.

Asbestos fibers are highly cytotoxic to cultured mammalian cells and produce chromosomal aberrations in several rodent cell types. There is some uncertainty in the literature as to whether these fibers are clastogenic to cultured human cells. Asbestos fibers do not produce either DNA damage or back mutations in prokaryotic assay systems, and they do not appear to cause DNA strand breaks in either rodent or human cells. The evidence that these fibers can produce either forward mutation or neoplastic transformation of mammalian cells is weak. Asbestos fibers are clearly oncogenic to humans and animals, but, except for clastogenic effects in rodent cells, there is little evidence for genotoxicity of fibers. It is reasonable to expect, therefore, that these materials may be oncogenic by virtue of mechanisms rather than as tumor initiators.

Animals↗
PubMed1983

DNA adduct formation by 7,12-dimethylbenz[a]anthracene and its noncarcinogenic 2-fluoro analogue in female Sprague-Dawley rats.

The potent polycyclic aromatic hydrocarbon 7,12 dimethylbenz[a]anthracene (DMBA) bound to the DNA of numerous organs of the female outbred Sprague-Dawley rat after iv administration under a regimen known to produce a high yield of mammary adenocarcinomas. The maximum DNA binding levels observed following iv administration of 5 mg (20 mumol) DMBA range from approximately 12 mumol hydrocarbon/mol deoxyribonucleic for the liver to approximately 5 mumol hydrocarbon/mol deoxyribonucleotide for the mammary gland, the target tissue. Administered under identical conditions, the noncarcinogenic analogue 2-fluoro-7,12-dimethylbenz[a]anthracene (2F-DMBA) bound to the DNA at levels of about 5-10% that of DMBA (i.e., 0.3-1.6 mumol/mol deoxyribonucleotide). Chromatographic analysis of the hydrocarbon-deoxyribonucleoside adducts produced showed that for DMBA at least two major types of identifiable adducts were observed in all tissues examined, the major one being that resulting from the reaction of a DMBA bay-region diol-epoxide. The other adduct type resulted from the binding of an analogous diol-epoxide of a DMBA metabolite, 7-hydroxymethyl-12-methylbenz[a]anthracene. Adducts from 2F-DMBA were observed on high-pressure liquid chromatography but were in quantities insufficient for characterization. The finding of higher levels of chromatographically identical DMBA-DNA adducts in the nontarget (liver) tissue than in the target tissue indicated that adduct formation per se was not a sufficient stimulus for the cancer induction. However, the failure of the structurally similar 2F-DMBA, which produced only very low levels of DNA adducts, to induce mammary cancer implies that certain levels of carcinogen-DNA adducts may be necessary for carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

In vitro metabolism of selected fluoro analogs of 7,12-dimethylbenz[a]anthracene.

We have compared the metabolite profiles generated from the rat liver incubation of monofluorinated derivatives of 7,12-dimethylbenz[a]anthracene. These monofluoro analogs are known to exhibit varying degrees of carcinogenicity. In this study we observed that the presence of fluorine substituents blocked metabolism at the fluorinated positions, some of which may be critical for biological activity. Furthermore, we also found that the fluorine substituents affected the chemical reactivity of the 5,6-arene oxide metabolites in terms of their ability to undergo methanolysis.

9,10-Dimethyl-1,2-benzanthracene↗