| The development of asbestos related disease in | | | | significant DNA fragmentation in a 24-h culture. Neither |
| workers has been closely studied for some time. | | | | CHR nor CRO caused DNA ladder formation in 24-h |
| However, a new wave of mesothelioma cases are | | | | cell cultures. However, in 48-h cell cultures, both CHR- |
| emerging from the spouses of workers that were | | | | and CRO-exposed cells, but not WOL, resulted in the |
| exposed to this hazardous material. One important | | | | formation of DNA ladders characteristic of apoptosis. |
| study is called, "Asbestos-Related Disease from | | | | In summary, these results suggest that, unlike |
| Household Exposure" by Gary R. Epler, Muiris X. Fitz | | | | nonfibrogenic particulates, low doses of asbestos |
| Gerald, Edward A. Gaensler, Charles B. Carrington - | | | | fibers cause apoptosis in cultured human AM that may |
| Respiration 1980;39:229-240. Here is an excerpt: | | | | be an early step in the development of lung fibrosis." |
| "Abstract - The importance of nonoccupational | | | | A third study is called, "Iron mobilization from crocidolite |
| asbestos exposure has been emphasized recently. To | | | | asbestos greatly enhances crocidolite-dependent |
| illustrate this problem, we report 4 persons with | | | | formation of DNA single-strand breaks in øX174 RFI |
| asbestos-related disease from household exposure. | | | | DNA" by Loren G. Lund and Ann E. Aust - Department |
| There were 2 wives of asbestos workers, who | | | | of Chemistry and Biochemistry, Utah State University |
| cleaned their husbands' work clothes. One developed | | | | Logan, UT 84322–0300, USA. Here is an excerpt: |
| a mesothelioma and the other plaques, calcification, | | | | "The ability of the iron associated with asbestos to |
| benign asbestos pleural effusion and subpleural | | | | catalyze damage to øX174 RFI DNA was |
| parenchymal fibrosis. 2 men were exposed as children | | | | determined and compared with iron mobilized from |
| while playing in a cellar room which was also used for | | | | asbestos. Asbestos (1 mg/ml) suspended for 30 min in |
| their father's muffler repair business. At ages 27 and | | | | 50 mM NaCl containing 0.5 µg øX174 RFI DNA, pH |
| 33, they had pleural and diaphragmatic calcifications." | | | | 7.5, did not catalyze detectable amounts of DNA |
| Another study worth examining is called, "Asbestos | | | | single-strand breaks (SSB). However, addition ofo |
| induces apoptosis in human alveolar macrophages" by | | | | ascorbate (1 mM) resulted in 19, 26, 7 or 8% DNA with |
| R. F. Hamilton, L. L. Iyer and A. Holian - Department of | | | | SSB for crocidolite, amosite, chrysotile or tremolite |
| Internal Medicine, University of Texas Medical School, | | | | respectively. The percentage of DNA with SSB |
| Houston 77030, USA. Am J Physiol Lung Cell Mol | | | | induced by each form of asbestos was directly |
| Physiol 271: L813-L819, 1996. Here is an excerpt: | | | | related to its iron content. Inclusion of desferrioxamine |
| "Asbestos refers to a group of fibrous minerals | | | | B, which binds Fe(III) rendering it redox inactive, |
| implicated in the development of several lung diseases, | | | | completely inhibited asbestos-dependent formation of |
| including fibrosis (asbestosis), cancer, and malignant | | | | DNA SSB, suggesting that iron was responsible for |
| mesothelioma. Although major health risks exist in | | | | catalyzing the formation of DNA SSB. Mobilization of |
| occupationally exposed individuals, low-level exposures | | | | Fe(II) from crocidolite by citrate, EDTA or |
| of asbestos may still contribute to health problems. | | | | nitrikrtriacetate (1 mM) in the absence of ascorbate |
| The mechanism by which asbestos causes lung | | | | resulted in 15, 33 or 63% DNA with SSB respectively. |
| disease is not clearly understood but has been | | | | This activity was completely inhibited by compounds |
| proposed to involve the alveolar macrophage (AM). | | | | considered to be OH scavengers, i.e. mannitol, 5, |
| We propose that asbestos induces apoptosis of AM, | | | | 5-dimethyl-l-pyroline N-oxide or salicylate (100 mM). |
| resulting in the development of an inflammatory state. | | | | Preincubation of crocidolite with citrate (1 mM) for 24 h |
| In this study, we examined two forms of asbestos, | | | | resulted in mobilization of 52 µM iron and increased |
| chrysotile (CHR) and crocidolite (CRO), along with a | | | | ascorbate-dependent induction of DNA SSB |
| control fiber, wollastonite (WOL), to characterize their | | | | compared with crocidolite that was preincubated |
| relative cytotoxicity and ability to stimulate apoptosis in | | | | without citrate. Iron mobilized by citrate was entirely |
| vitro. AM were cultured for 24 h with these | | | | responsible for crocidolite-dependent formation of DNA |
| particulates and examined for cell viability (trypan blue | | | | SSB as evidenced by complete inhibition with |
| exclusion) and apoptosis (morphology, levels of | | | | desferrioxamine B. Therefore, the results of the |
| cytosolic oligonucleosomal DNA fragments, and DNA | | | | present study strongly suggest that iron was |
| ladder). In the absence of a decrease in cell viability, | | | | responsible for asbestos-dependent generation of |
| both CHR and CRO produced changes in cell | | | | oxygen radicals, which resulted in the formation of |
| morphology consistent with apoptosis. In addition, levels | | | | DNA SSB. Mobilization of iron by chelators, followed by |
| of cytoplasmic oligonucleosomal DNA (Cell Death | | | | redox cycling, greatly enhanced crocidolite-dependent |
| Detection enzyme-linked immunosorbent assay) were | | | | formation of DNA SSB. Thus, mobilization of iron in |
| significantly enhanced for CHR (3-25 micrograms/ml) | | | | vivo by low mol. wt chelators may lead to the |
| and CRO (25-75 micrograms/ml) in a dose-dependent | | | | increased production of reactive oxygen species |
| manner (a process that was inhibitable by 10 microM | | | | resulting in damage to biomolecules, such as DNA." |
| Z-Val-Ala-Asp fluoromethyl ketone, an | | | | If you found any of these excerpts, please read them |
| interleukin-converting enzyme inhibitor). In contrast, | | | | in their entirety. We all owe a debt of gratitude to |
| WOL (up to 400 micrograms/ml) produced no | | | | these researchers. |