Chemical production of excited states. Chemiluminescence of carcinoginic hydrocarbons accompanying their metabolic hydroxylation and a proposal for common active site geometries for hydroxylation

Conference · Thu Sep 23 04:00:00 EDT 1976 · J. Phys. Chem.; (United States)

OSTI ID:7128339

Seliger, H H; Hamman, J P

A mechanism is proposed whereby metabolically produced epoxides of polycyclic aromatic hydrocarbons may be subject to an adventitious oxygenation, resulting in ring-opened carbonyl residues in excited electronic states. These carbonyl excited states may be assayed by light emission despite their low quantum yeilds of fluorescence. The intensities of chemiluminescence of the carcinogens benzo(a)pyrene, dibenz(a,h)-anthracene, and 3-methylcholanthrene, incubated with rat liver microsomes in the presence of cofactors, are correlated with the initial rates of hydroxylation of these parent compounds by the induced cytochrome P-448 system. The chemiluminescence intensity may be a tracer for the concentration of reactive epoxides formed during the metabolism of aromatic carcinogens. It is proposed that the preponderant fraction of the excited state carbonyl products that do not deexcite by light emission can add covalently to cellular macromolecules; a dark chemical analogue of the photochemical reactions of carbonyls. It is proposed that the metabolic products of all polycyclic aromatic hydrocarbons can be produced through three active site geometries. Carcinogens can be characterized by two of these three geometries. This common geometry mechanism and the predictions of chemiluminescence are consistent with the reported carcinogenicities of the fluoranthenes and can be extended toinclude the activating effects of methyl and amino substituents to noncarcinogenic or weakly carcinogenic parent polycyclic aromatic hydrocarbons. In particular, it can be applied to explain the carcinogenicity of 7,8-epoxybenzo(a)pyrene and the lack of carcinogenicity of the 9,10-oxide.

• Research Organization: Johns Hopkins Univ., Baltimore
• OSTI ID: 7128339
• Conference Information: Journal Name: J. Phys. Chem.; (United States) Journal Volume: 80:20
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400301* -- Organic Chemistry-- Chemical & Physicochemical Properties-- (-1987)
550200 -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
CARCINOGENS
CHEMILUMINESCENCE
ENERGY LEVELS
EXCITED STATES
HYDROCARBONS
HYDROXYL RADICALS
LUMINESCENCE
METABOLISM
ORGANIC COMPOUNDS
RADICALS