Effects of asbestos, iron oxide, silica, and carbon black on the microsomal availability of benzo[a]pyrene

Abstract

Particulate matter and polynuclear aromatic hydrocarbons are known to be cocarcinogenic. Using fluorescence spectroscopy, we determined that adsorption of benzoic] pyrene (BP) to iron oxide, silica, and asbestos (anthophyllite and Canadian chrysotile) results in a greatly enhanced rate of BP uptake into rat liver microsomes when compared to uptake from aqueous dispersions of BP microcrystals. Simple mixtures of BP microcrystals and particulates do not display enhanced microsomal uptake rates, an observation which indicates that adsorption of BP to the surface of the particle is necessary for enhanced microsomal uptake. BP was not released into microsomes from carbon black. Most importantly, the data indicate that asbestos particles are more effective than silica and iron oxide in enhancing the microsomal availability of BP. These observations suggest that particles, and especially the fibrous mineral particulates, could be cocarcinogenic as a result of their ability to adsorb polynuclear aromatic hydrocarbons and to transport these carcinogens into cells. Except for chrysotile, the particles did not disrupt microsomal integrity as determined by NADPH-dependent lipid peroxidation activity. Binding of the microsomes to the particles did not affect the BP uptake rates. In addition, these BP uptake rates were independent of both the concentrations of microsomes and of particles. These observations are consistent with the mechanism of particle-enhanced transport being an increased rate of BP solubilization from the adsorbed state into the aqueous phase, followed by rapid partitioning of BP into the microsomal membranes. Polynuclear aromatic hydrocarbons (PAH)1 are known human and animal carcinogens, and carcinogenesis by these compounds requires metabolic activation (Heidelberger, 1975;Sims & Grover, 1974). This activation occurs in the microsomal fraction of cells (Sims et al., 1974; Yang et al., 1977). Inhaled and instilled particulate matter is known to increase the carcinogenic potency of the PAH in lung tissue. For example, intratracheal instillation of benzo [a] pyrene (BP)results in only a low incidence of lung cancer (Saffiotti et al., 1965) unless particulates are also instilled. The known cocarcinogenic particulates include hematite or iron oxide (Saffiotti et al., 1968), asbestos (Pylev & Shabad, 1973), aluminum and titanium oxide (Stenback et al., 1976), and India ink (Pylev, 1961). In humans, cigarette smoking and asbestos inhalation are known to be highly cocarcinogenic (Selikoff et al.,

Presentation of benzo(a)pyrene to microsomal enzymes by asbestos fibers in the Salmonella/mammalian microsome mutagenicity test.

“…Our results and those of Lakowicz et al (10)(11)(12) showed that chemical carcinogen is more readily accessible to the microsomal enzymes when it is presented as a compound adsorbed onto the particles, and we found that this phenomenon has a biological value at least in the Ames test. In view of data presented above, the amplifying effect of asbestos exposure and cigarette smoking on the incidence of lung cancer (16) is clearly understandable.…”

“…Our results are easily understandable in the light of work done by Lakowicz et al (10)(11)(12), which showed that adsorption of BaP onto asbestos or other particles increases membrane uptake of BaP. This was not related to the specific minerological character of different types of asbestos (10).…”

“…This was not related to the specific minerological character of different types of asbestos (10). Amosite, crocidolite and chrysotile were equally effective in BaP presentation (Figs.…”

“…All these data suggest that asbestos fibers do not act primarily as genotoxic carcinogens inducing alteration in DNA but rather play the role of cofactor. In favor of this hypothesis are recent papers showing an enhancing effect of asbestos fibers on solubilization and dispersion of benzo(a)pyrene (BaP) in the lipid bilayer of the cellular membrane (10,11 …”

Effects of Crocidolite and Chrysotile Asbestos on Cellular Uptake and Metabolism of Benzo(a)pyrene in Hamster Tracheal Epithelial Cells

“…Our results are supported by studies of Lakowicz and colleagues who document by fluorimetry the increased transport of BaP to artificial membranes and microsomes when the hydrocarbon is adsorbed on a variety of particulates (16)(17)(18). Dispersions and particles of BaP do not transfer readily to membranes indicating an important, although undefined, role of the "carrier" mineral.…”