Effects of ultraviolet radiation on 3,4-benzpyrene and other polycyclic aromatic hydrocarbons; carcinogenic activity of aqueous extracts from irradiated 3,4-benzpyrene.
It was shown in preceding papers (2, 3) that when 3,4-benzpyrene dissolved in benzene was irradiated with monochromatic radiation of wave length 2,537 A. in the presence of oxygen, at least two water-soluble substances were included in the products and that these could be recognized, and some of their properties deduced, by spectrophotometric methods. The first, substance A, was characterized at pH 8 by an absorption band whose maximum intensity was at 3,600 A. It was labile, readily taking up atmospheric oxygen irreversibly when its aqueous solutions were allowed to stand at room temperature; but it could be stabilized by cooling them to 0 ~ C. and storing them in an atmosphere of nitrogen. The second substance, B, absorbed at 2,760 A. and was more stable to oxygen, but it was destroyed by strong alkali. It reacted readily with glutathione and with other compounds containing sulfhydryl groups. Water-soluble oxidation products of 3,4-benzpyrene are of course well known. A monohydroxy derivative is excreted as a metabolite when the hydrocarbon is fed to rats (8, 13); and a photoderivative has been described that has the power to inhibit respiratory enzymes (6, 7). None of them, however, has been reported to have any carcinogenic activity. Rideal and Schulman have shown (12) that materials very similar to, if not identical with, substances ,4 and B are readily adsorbed onto protein monolayers, and so might be expected to pass more readily than the unadsorbed hydrocarbon through cell membranes. By analogy with hemolytic substances, which they showed to possess this property to a high degree, substances ,4 and B might thus be expected to be biologically active. Other observations recorded in the literature, which were summarized in the introduction to Part I, seem to support this view. Since the absorption bands of ,4 and B do not accord with those of any derivative
Effects of ultraviolet radiation on 3,4-benzpyrene and other polycyclic aromatic hydrocarbons; absorption spectra and some chemical properties of the water-soluble products.
Under the influence of ultraviolet radiation, especially in the presence of oxygen, the polycyclic aromatic hydrocarbons undergo various chemical changes, such as the well known polymerization of anthracene to dianthracene (34), or the production of photo-oxides (15, 16, 22). Some of the photo-oxidation products are soluble in water, and Boyland (7, 8) has investigated their effects on respiratory enzymes. Rideal and Schulman (39) have suggested that such watersoluble derivatives might play some part in the biological effects produced by the hydrocarbons, as they found that when the products of irradiation of a benzene solution of 3,4-benzpyrene were extracted with water, some constituent of the aqueous solution was readily adsorbed onto a protein monolayer, and might therefore be expected to pass into a living cell more readily than does the unadsorbed parent substance. A number of observations recorded in the literature lend support to this view. Lewis (32) found that when tissue cultures growing in a medium containing carcinogenic hydrocarbons were exposed to intense light on the microscope stage cell division was inhibited, and that when mitosis was restored again in the dark it resulted in abnormalities resembling those seen in malignant growths. Earle and Voegtlin (23), in similar experiments in which all but extreme red light was carefully excluded, found less degeneration in their experimental cultures than in control cultures treated with carcinogens in the presence of light. Creech (18, 19) has produced many abnormal mitoses in tissue cultures by adding the water-soluble choleic acid derivatives of carcinogenic hydrocarbons (24) to the culture medium. Mention must also be made of the extensive work of Mottram (37) on the photodynamic effect of carcinogenic hydrocarbons on infusoria; and of an t)bservation by Hollaender and
Sterol metabolism. XLI. Cholesterol A-ring autoxidations
Abstract Chromatographic and spectral evidence is adduced for the presence of cholest-5-en-3-one, cholest-4-en-3-one, and cholest-4-ene-3,6-dione in samples of cholesterol aged naturally in air or subjected to irradiation in air by 60 Co gamma radiation. These findings establish an additional mode of air oxidation of cholesterol to A-ring 3-ketones. Moreover, the oxidation by air of cholest-5-en-3-one induced by 60 Co gamma radiation yielded cholest-4-en-3-one, cholest-4-ene-3,6-dione, and the epimeric 3-oxocholest-4-ene-6-hydroperoxides. Cholest-4-en-3-one was not altered by irradiation in air, nor was cholesterol isomerized to cholest-4-en-3β-ol upon irradiation. From these observations it is deduced that the radiation-induced A-ring dehydrogenation of cholesterol yields initially cholest-5-en-3-one which upon isomerization yields cholest-4-en-3-one not further oxidized and which by a second oxidation yields the epimeric 3-oxocholest-4-ene-6-hydroperoxides which decompose to cholest-4-ene-3,6-dione.