Use of the Syrian Hamster Embryo Cell Transformation Assay for Determining the Carcinogenic Potential of Heavy Metal Compounds

Abstract

Cobalt sulfate hydrate, gallium arsenide, molybdenum trioxide, vanadium pentoxide, and nickel sulfate heptahydrate were tested in the Syrian hamster embryo (SHE) assay in order to increase the SHE assay database for heavy metals. All five compounds produced significant morphological transformation at one or more doses in a dose-responsive manner. Cobalt sulfate hydrate, gallium arsenide, molybdenum trioxide, and nickel (IT) sulfate heptahydrate were all positive with a 24-hr exposure, suggesting direct DNA perturbation. Vanadium pentoxide was negative with a 24-hr exposure, but positive with a 7-day exposure. This pattern of response (24-hr SHE negative/7-day SHE positive) has been seen with other chemicals which have tumor promotion-like characteristics. Since the inception of the use of the SHE cell transformation assay for detecting the neoplastic transformation potential of chemicals, over 42 heavy metal compounds have been tested in this assay. Based on the 24 metal compounds which have been tested in the SHE, Salmonella, and some type of rodent bioassay, the SHE assay is 92% concordant with rodent bioassay carcinogenicity results, including a sensitivity of 95% (21/22) and a specificity of 50% (1/2). At this time, the measure of SHE assay specificity for rodent carcinogenicity of metals is limited by the paucity of metal compounds which are rodent noncarcinogens. The Salmonella assay results are only 33% concordant with the rodent bioassay for these same chemicals. This relatively high concordance between the SHE assay and the rodent bioassay carcinogenicity results demonstrates the utility of the SHE assay for determining the carcinogenic potential of heavy metal compounds in rodent Cancer bioaSSays. C 1996 Soday of Toxicology.In 1963 Berwald and Sachs described the in vitro morphological transformation of normal Syrian hamster embryo cells to tumor cells by carcinogenic chemicals (Berwald and Sachs, 1963). Since that time the Syrian hamster embryo (SHE) cell in vitro transformation assay has been used by numerous investigators to test the transforming potential of over 472 chemical/physical agents. Of these 472 chemicals, over 200 have been tested in the standard rodent bioassay, giving a sensitivity of 82% (146/177), a specificity of 69% (25/36), and an 80% concordance (171/213) between the results of these two tests. Using a modification of the original SHE assay protocol, which is principally a reduction in the culture medium pH from 7.3 to 6.7, we have tested 48 chemicals for their SHE cell transformation potential. The concordance between the reduced pH SHE assay and the rodent bioassay for these 48 chemicals is 85% (41/48), including a sensitivity of 87% (26/30) and a specificity of 83% (15/ 18). Importantly, although rodent noncarcinogens are fewer in number than rodent carcinogens, the SHE assay specificity for the rodent bioassay is greater than 80%.The purpose of the present study was to test the transformation potential of five metal compounds: cobalt sulfate hydrate, gallium arsenide, molybde...

Effects of Vanadium Pentoxide on the Histological and Sperm Parameters of Male Guinea Pigs

“…Vanadium compounds have been shown to cause an induction of structural and numerical chromosome aberrations (Milgliore et al, 1993), marked increase in cell transformation, indicating positive increase in genotoxicity of the system (Rivedal et al, 1996;Kerckaert et al, 1996).V 2 O 5 caused reduction in airflow in central and peripheral air ways and an increase in absolute number and relative percentage of polymorpholonuclear leucocytes (Knecht et all., 1992), neutrophil influx ( Pierce et al, 1996), intense pulmonary inflammatory cytokine mRNA expression (Pierce et al, 1996), increase in the frequency of micronucleus formation in mice (Si et al 1982) formation of DNA protein cross-links (Cohen et al, 1992) and an increase in DNA migration (Milgliore et al, 1993), indicating DNA damaging potential of vanadium pent oxide (Rojas et al, 1996). These effects of V 2 O 5 may be due to an effect on Na/K + ATPase antiport system which affects the Ca 2+ metabolism of tissues and organs ( Ringelband and karbe 1996), oxidative effects through apoptosis and necrosis (Nangi and Hiller 1997), a mass mobilization of Ca 2+ from the intracellular cells ( Zhang et al, 1993) , sensitization and cell damage from lysis.…”

Nickel Toxicity and Carcinogenesis

“…In rodent cells, which transform more easily than human cells, the insoluble compounds act like complete carcinogens. For example, in Syrian hamster embryo (SHE) cells, Ni 3 S 2 induced morphological transformation, growth in soft agar, and development of tumors upon injection to nude mice [297]. In the same cells, soluble nickel was less potent and produced only fast-growing immortalized colonies [298], although at equitoxic doses, insoluble Ni 3 S 2, NiO, Ni 2 O 3 , and soluble nickel acetate showed equal transforming effects in BHK-21 cells [299].…”

Environmental epigenetics in metal exposure

“…5,6 However, most of these metals, with the exception of chromium, are mildly mutagenic or non-mutagenic in conventional bacterial and mammalian mutagenesis assays. 7,8 Their ubiquitous and indestructible nature makes these metals the most resilient form of environmental pollutants. While it is thought that these metals disturb a vast array of cellular processes, such as redox state and various intracellular stress-signaling pathways, their ability to induce diseases remains poorly understood.…”