tremolite and Cell-Transformation--Neoplastic

Asbestos was abundantly used in industry during the last century. Currently, asbestos confers a heavy social burden due to an increasing number of patients with malignant mesothelioma (MM), which develops after a long incubation period. Many studies have been conducted on the effects of the asbestos types that were most commonly used for commercial applications. However, there are few studies describing the effects of the less common types, or minor asbestos. We performed a rat carcinogenesis study using Japanese tremolite and Afghan anthophyllite. Whereas more than 50% of tremolite fibers had a diameter of < 500 nm, only a small fraction of anthophyllite fibers had a diameter of < 500 nm. We intraperitoneally injected 1 or 10 mg of asbestos into F1 Fischer-344/Brown-Norway rats. In half of the animals, repeated intraperitoneal injections of nitrilotriacetate (NTA), an iron chelator to promote Fenton reaction, were performed to evaluate the potential involvement of iron overload. Tremolite induced MM with a high incidence (96% with 10 mg; 52% with 1 mg), and males were more susceptible than females. Histology was confirmed using immunohistochemistry, and most MMs were characterized as the sarcomatoid or biphasic subtype. Unexpectedly NTA showed an inhibitory effect in females. In contrast, anthophyllite induced no MM after an observation period of 550 days. The results suggest that the carcinogenicity of anthophyllite is weaker than formerly reported, whereas that of tremolite is as potent as major asbestos as compared with our previous data.

Topics: Animals; Asbestos, Amphibole; Carcinogenicity Tests; Cell Transformation, Neoplastic; Female; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Nitrilotriacetic Acid; Particle Size; Rats; Rats, Inbred BN; Rats, Inbred F344; Risk Assessment; Risk Factors; Sex Factors; Time Factors

Samples of Metsovo-tremolite asbestos, previously found to be the causative agent of endemic pleural calcification and an increased level of malignant pleural mesothelioma in a rural area of north-western Greece (Metsovo area), were tested in various in vitro toxicity test systems. It was found that asbestos fibres of this type were strong inducers of micronuclei and numerical chromosomal abnormalities while they induced low levels of chromosomal aberrations in mammalian cells in culture. Furthermore, this type of asbestos can induce a low level of in vitro transformation of Syrian hamster embryo cells. The fibres had no effect on gap-junctional cell-cell communication (followed by the dye-transfer method) and did not induce any mutations in the Salmonella typhimurium strain TA102 which is known to be sensitive to the action of various oxidative agents. These results support the hypothesis generated from studies on other types of asbestos that such fibres induce tumours by causing chromosomal mutations.

Topics: Aneuploidy; Animals; Asbestos; Asbestos, Amphibole; Cell Communication; Cell Line; Cell Transformation, Neoplastic; Chromosome Aberrations; Cricetinae; Cricetulus; Greece; Humans; Incidence; Mesocricetus; Mesothelioma; Micronucleus Tests; Mutagenesis; Mutagenicity Tests; Pleural Neoplasms; Salmonella typhimurium; Silicic Acid