Neoplastic transformation by quartz in the BALB/3T3/A31‐1‐1 cell line and the effects of associated minerals

Abstract

Quartz, the most common form of crystalline silica, was tested quantitatively for neoplastic transformation in the mouse embryo cell line, BALB/3T3/A31-1-1. Five quartz dust samples of respirable size [Min-U-Sil 5 (MQZ); hydrofluoric-acid-etched MQZ (HFMQZ); Chinese standard quartz (CSQZ); DQ12; and F600] all induced significant levels of neoplastic transformation, showing dose-dependent increases in the frequency of morphologically transformed foci at lower tested doses and a plateau level of response at higher doses. The plateau levels reached by the five tested samples did not differ substantially (maximum transformation frequencies per 10(5) cells ranging from 53.2 for MQZ to 28.3 for HFMQZ). F600 had minimal cytotoxicity but transforming activity comparable to the other samples. Cells from all tested transformed foci, when injected s.c. in nude mice, grew as sarcomas. Cytogenetic analysis showed that all tested silica-transformed cell lines had acquired one to five additional marker chromosomes, of types not seen in untreated control lines, indicative of induced chromosomal translocations and amplification. Increased expression of one or more of five genes (p53, myc, H-ras, K-ras, and abl) was observed in several quartz-transformed cell lines. No transforming activity was found for hematite and anatase (both nontoxic), and for rutile (more toxic than MQZ). Combined exposure (1:1 w/w per unit culture area) of each of these dusts with MQZ showed that hematite and anatase inhibited MQZ toxicity as well as transformation, whereas rutile markedly enhanced MQZ toxicity but not MQZ-induced transformation.

Unveiling the Variability of “Quartz Hazard” in Light of Recent Toxicological Findings

“…Both treatments do indeed modify the silanol distribution. Similarly, a rough correspondence can be noted between the evaluated toxicity and the expected abundance of reactive silanols in those studies where a different biological activity among silica specimens was reported. − ,− ,− Here, we would like to discuss the most obvious questions that our proposal may elicit.…”

“…Many studies showed that crystalline silica particles are cytotoxic, inflammogenic, trigger the production of inflammatory substances, oxidants and growth factors from cells, can damage membranes, etc. , However, when the same test was performed on a variety of silica samples either collected or prepared ad hoc, the extent and even the nature of the cellular response varied. ,− If the quartz particles were associated with other minerals or elements (such as aluminum, iron, and carbon), effects were in some cases enhanced − or blunted in others. ,− Also, deposition of polymers or other substances on the particle surface modified (mostly inhibited) cellular responses. − …”

Summary of Notifiable Noninfectious Conditions and Disease Outbreaks: Surveillance for Silicosis — Michigan and New Jersey, 2003–2010

“…The ability of quartz to induce dose-dependent morphological transformation of cells in vitro has been demonstrated in experiments with Syrian hamster embryo cells and mouse embryo BALB/c-3T3 cells [Saffiotti and Ahmed 1995]. Gu and Ong [1996] also reported a significant increase in the frequency of transformed foci of mouse embryo BALB/c-3T3 cells after treatment with Min-U-Sil-5 quartz.…”

Silica, crystalline: quartz dust, cristobalite dust and tridymite dust (respirable fraction) [MAK Value Documentation, 2000]

“…After inoculation into naked mice of cells which had been transformed by Min-U-Sil 5, by hydrofluoric acid-etched Min-U-Sil 5 or by Sikron F 600, in each case 5/5 animals developed fibrosarcomas. In some of the transformed cell lines, the expression of oncogenes was shown to be increased (Saffiotti and Ahmed 1995); this could be evidence of the induction of gene amplification. Concentration-dependent increases in cell transformation rates were seen in SHE cells treated with Min-U-Sil and α-quartz from concentrations of 2 and 10 µg/cm 2 , respectively (Hesterberg and Barrett 1984).…”