Anthracene, carcinogenic activity

Angstrom units, definition, 128 Anthracene, carcinogenic activity, 45 Anthracenedihydrodiols, synthesis, 45 Arylnitrones, reaction mechanism, 363f... 

Since the spectrum of dibenz [ ,]i]anthracene was not identical to that of the carcinogenic tars, carcinogenic activity obviously was not confined to a unique chemical structure and indeed Cook, who had joined this research effort in 1929, soon synthesized a number of new hydrocarbons, and many of these were carcinogenic. 

Table I. Effect of a Methyl Group at a Single Starred Position on Carcinogenic Activity of Benz[a]anthracene Derivatives...

This list includes BP, 7,12-dimethylbenz[a]anthracene, 3-methylchol-anthrene, dibenzo[a,i]pyrene and dibenzo[a,h]pyrene. These PAH can be activated both by one-electron oxidation and/or monooxygenation. There are a few PAH with low IP which are inactive (Table I), such as perylene, or weakly active, such as anthanthrene. This indicates that low IP is a necessary, but not sufficient factor for determining carcinogenic activity by one-electron oxidation. These inactive or weakly active PAH have the highest density of positive charge delocalized over several aromatic carbon atoms in their radical cations, whereas the active PAH with low IP have charge mainly localized on one or a few carbon atoms in their radical cations. 

Rice, J.M., Joshi, S.R., Shenefelt, R.E., Wenk, M. (1978). Transplacental carcinogenic activity of 7, 12-dime-thylbenz(a)anthracene. In Carcinogenesis, Vol. 3. Polynuclear... 

A single dose of 0.05 mg/kg dibenz[a,h]anthracene in polyethylene glycol (PEG)-400 failed to induce tumors in male Swiss mice after 30 weeks. However, forestomach papillomas were found in 10% of mice administered a single dose of 0.05 mg/kg dibenz[a,h]anthracene followed by 30 weekly doses of PEG alone, and in 21 % of the mice when the dibenz[a.h]anthracene dose was followed by 30 weekly doses of PEG plus 3% croton oil (Berenblum and Haran 1955). Treatment with croton oil alone yielded a 14-16% tumor incidence. These results suggest that the carcinogenic activities of croton oil and dibenz[a,h]anthracene are additive in the mouse forestomach. 

Boyland E, Sims P. 1967. The carcinogenic activities in mice of compounds related to benz(a )anthracene. Int J Can 2 500-504. 

W5. Watabe, T., Fujieda, T., Hiratsuka, A., Ishizuka, T., Hakamata, Y., and Ogura, K., The carcinogen, 7-hydroxymethyl-12-methyl benz(a)anthracene, is activated and covalently binds to DNA via a sulphate ester. Biochem. Pharmacol. 34, 3002-3005 (1985). 

Flesher and Myers (1990) have correlated carcinogenic activity of benzo[a]anthracene to its bioalkylation at the site of injection. Male rats were dosed subcutaneously and the tissue in contact with the hydrocarbon was visualized after 24 hours under UV light. 

Flesher, J. W., and S. R. Myers. 1990. Bioalkylation of benz(a)anthracene as a biochemical probe for carcinogenic activity. Lack of bioaUcylation in a series of six noncarcino-genic polynuclear aromatic hydrocarbons. Drug Metab. Dispos. 18(2) 163-67 cited in Chem. Abstr. CA 113(3) 19245g. 

Several polycyclic aromatic hydrocarbons that are genotoxic were ozonized in acetone-water or dimethylsulfoxide-water solvents. In most cases, mutagenic or carcinogenic activity was entirely lost after a brief exposure to ozone, but in one case (7,12-dimethylbenz[a]anthracene, 82) a small number of animal tumors developed. 

Table 4.3. COMPARISON OF CARCINOGENIC ACTIVITY IN DlMETHYL-BENZfflJ ANTHRACENES WITH ACTIVITIES OF THE TWO ANALOGOUS MONOMETHYL-...

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