Abstract

The involvement of catalytic iron in the vitro activities of crocidolite asbestos has been investigated. Exposure of C3H10T1/2 cells to either the UICC crocidolite standard reference sample or a non fibrous (milled) derivative resulted in an increase of thiobarbituric acid reactive substances. This catalytic activity was inhibited by pretreatment with the iron chelator desferrioxamine. The effect of this activity on cellular DNA was measured in an assay based on the production of DNA-strand breaks. Increased levels of DNA-strand breaks were detected in cultures treated with both the milled and UICC crocidolite. Inclusion of desferrioxamine with the asbestos inhibited DNA-strand breakage. It is concluded the catalytic iron present on the dust is capable of damaging both lipid and DNA and that this could be an important mechanism in asbestos pathogenicity.

Highlights

  • In gene mutation assays asbestos has produced negative results (Chamberlain & Tarmy, 1977; Reiss et al, 1982) while in one study it was found to be weakly mutagenic towards the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus of Chinese hamster lung cells (Huang, 1979)

  • Asbestos contains iron in its lattice structure which could participate in the production of thiobarbituric acid reactive substances (TBARS)

  • To investigate this hypothesis cultures of C3H1-OTl cells were treated with asbestos which had been pretreated with desferrioxamine, a specific iron chelator

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Summary

Introduction

In gene mutation assays asbestos has produced negative results (Chamberlain & Tarmy, 1977; Reiss et al, 1982) while in one study it was found to be weakly mutagenic towards the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus of Chinese hamster lung cells (Huang, 1979). Other investigators have reported increases in sister chromatid exchanges (Livingston et al, 1980; Babu et al, 1981), while others have found no increase (Price-Jones et al, 1980). Asbestos fibres have been shown to cause morphological transformation in some systems, for example Syrian hamster embryo cells (Hesterburg & Barrett, 1984) but not C3H10T1 cells (Brown et al, 1983). A number of other studies have demonstrated an increase in chromosomal aberrations including breaks, fragmentation and aneuploidy (Sinnock & Seabright, 1975; Huang et al, 1978)

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