asbestos--crocidolite and Fibrosarcoma

An implant can act as a physical carcinogen. Chemicals applied to its surface can augment that. To explore if cocarcinogenesis would affect the incidence of tumour on implants, we tested several physical (asbestos, beta irradiation) and chemical (acridine orange, phorbol methyl ester, cigarette smoke tar, extract of Agaricus bisporus mushroom) carcinogens on 25 mm diameter nitrocellulose filters implanted in groups of BALB/c mice in 9 experiments. Saline was applied in 287 concurrent controls. Irradiation by 540 kBq I-125 fibrinogen on foreign bodies of surface area 20sq cm induced tumour in 6/6 pilot animals (expected 2/6) and in 25/36 animals (controls 13/29; p < 0.04). The mean dose (beta and gamma) to cells within 20 microm of the filter surface was estimated to be 782 mGy. Exposures to 270kBq or less were not significantly cocarcinogenic with single implants. Radiation from the paired implants was detectible up to 80 weeks. Asbestos, however, 2.3 or 4.6 mgm on implants did not in 3 trials increase sarcoma yield significantly, but did induce mesothelial-type growths in the peritoneum. Asbestos (2.3 mg) injected without an implant provoked no tumour at the site. The chemical carcinogen acridine orange gave ambiguous results, and the others reduced tumour incidence insignificantly. The irradiation history may be germane in the human cases that arise.

Topics: Animals; Asbestos, Crocidolite; Carcinogens; Cocarcinogenesis; Collodion; Fibrosarcoma; Humans; Male; Mice; Mice, Inbred BALB C; Micropore Filters; Prostheses and Implants; Radiation Dosage; Radiation, Ionizing

Supernatants from in vivo asbestos-activated macrophages failed to show any cytostatic activity against a syngeneic fibrosarcoma cell line in vitro. UICC chrysotile-induced peritoneal exudate cells also failed to demonstrate any growth inhibitory effect on the same cells in Winn assays of tumor growth. Mixing UICC crocidolite with inoculated tumor cells resulted in a dose-dependent inhibition of tumor growth; this could, however, be explained by a direct cytostatic effect on the tumor cells of high doses of crocidolite, which was observed in vitro.

Topics: 5'-Nucleotidase; Acid Phosphatase; Animals; Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Cell Division; Cell Membrane; Fibrosarcoma; Lysosomes; Macrophages; Mice; Mice, Inbred CBA; Nucleotidases; Time Factors