Elemental modifications and polycyclic aromatic hydrocarbon metabolism in human fibroblasts

Abstract

Mineral fibers and particulates represent one of the best documented, economically important, and ubiquitously occurring categories of human carcinogens. Yet, while a wealth of information exists concerning the mechanism of action of physical, chemical, and viral carcinogens, virtually nothing is known relative to the mechanism of action of this economically important class of carcinogenic compounds known as mineral fibers and particulates. While the length and diameter of various forms of asbestos have been associated with both cellular toxicity in vitro and tumor occurrence in vivo, nothing is known about whether or not these same physical properties are responsible for the purported synergistic interaction between cigarette smoking and asbestos exposure relative to the induction of bronchogenic carcinoma. Thus, while the risk of bronchogenic carcinoma for nonsmokers exposed to asbestos appears to be only slightly greater than that for unexposed nonsmoking populations, the risk of occurrence of this same tumor in asbestos workers who also smoke is approximately 100-fold greater than in nonsmoking asbestos workers. The risk of bronchogenic carcinoma is increased approximately 8-fold in asbestos workers who smoke over nonexposed smokers. Since it is clear that cigarette smoke contains over 150 polycyclic aromatic hydrocarbons, some of which are known animal carcinogens, and since other laboratories have reported that metals associated with asbestos redirect the metabolism of these agents, it was of interest to us to investigate the effects of mineral fibers on the metabolism and biochemistry of polycyclic aromatic hydrocarbons.

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

“…Thus, consistent with earlier results using NIEHS intermediate chrysotile (34,35), the simultaneous addition of NIEHS short chrysotile and B(a)P did not enhance, in a dose-dependent manner, the metabolism and subsequent DNA binding of the hydrocarbon in human fibroblasts. However, when the B(a)P-DNA adducts formed in the presence of 1 mg/mL NIEHS short chrysotile were compared by HPLC analysis with those generated in the absence of the fiber, the relative amounts of the various enantiomeric B(a)P-deoxyribonucleoside adducts appeared to be altered.…”

In Vitro Assessment of Asbestos Genotoxicity

“…This latter observation is of interest, since DiPaolo et al (36) have reported a synergism between asbestos fibers and BP with respect to SHE cell transformation. The simultaneous addition of NIEHS chrysotile and BP to normal human fibroblasts did not result in either increased BP metabolism (41,43,44), altered BP-metabolite profiles, cytotoxicity (41,43), BP-DNA binding levels (43,44), or in substantially altered BP-deoxyribonucleoside adduct profiles (44). These studies and others discussed by Mossman (45), may indicate that asbestos fibers act as the level of a cocarcinogen or promoter with respect to their oncogenic effects.…”

Thermal modification of chrysotile asbestos: evidence for decreased cytotoxicity.

“…Normal human fibroblasts (human foreskin, line 149) were cultured at the 16th or 17th passage in Eagle's minimum essential medium, supplemented with 10% fetal bovine serum (GIBCO) (21). Confluent fibroblast monolayers were harvested by trypsinization (0.01% trypsin in 0.01% EDTA) and dispersed in growth medium to achieve a single-cell suspension.…”