Species-specific Process Research Articles

Toxicological evaluation of pollutants in soil — concept of the AGU and assessment of tolerable concentrations for metals

Inhibition of gap junctional intercellular communication (GJIC) has been postulated as a nongenotoxic carcinogenic mechanism, probably related to tumor promotion. Recent studies assessed the role of GJIC in the induction of rodent liver tumors by high levels of phthalate esters. Studies with di(2-ethylhexyl) (DEHP) and diisononyl (DINP) phthalates demonstrated that inhibition of GJIC in rats and mice was well correlated with induction of both liver tumors and markers for peroxisomal proliferation. However, GJIC was unaffected in hamsters and primates, species in which phthalate treatment does not induce peroxisomal proliferation. In vitro studies which extended the database to include human liver cells mirrored the in vivo situation; GJIC was inhibited in rat and mouse cells but not in cells from unresponsive species including humans. Peroxisomal proliferation has been characterized as a species-specific process essential for phthalate-induced rodent liver tumor induction. That GJIC was not inhibited in primate liver or human liver cells provides evidence for a second species-specific carcinogenic process. Thus the GJIC data along with those from studies of peroxisomal proliferation support the view that the carcinogenic effects of DEHP and DINP in rodents are not relevant to humans.

Influence of glucose on arsenic toxicity in MDCK cells

Inhibition of gap junctional intercellular communication (GJIC) has been postulated as a nongenotoxic carcinogenic mechanism, probably related to tumor promotion. Recent studies assessed the role of GJIC in the induction of rodent liver tumors by high levels of phthalate esters. Studies with di(2-ethylhexyl) (DEHP) and diisononyl (DINP) phthalates demonstrated that inhibition of GJIC in rats and mice was well correlated with induction of both liver tumors and markers for peroxisomal proliferation. However, GJIC was unaffected in hamsters and primates, species in which phthalate treatment does not induce peroxisomal proliferation. In vitro studies which extended the database to include human liver cells mirrored the in vivo situation; GJIC was inhibited in rat and mouse cells but not in cells from unresponsive species including humans. Peroxisomal proliferation has been characterized as a species-specific process essential for phthalate-induced rodent liver tumor induction. That GJIC was not inhibited in primate liver or human liver cells provides evidence for a second species-specific carcinogenic process. Thus the GJIC data along with those from studies of peroxisomal proliferation support the view that the carcinogenic effects of DEHP and DINP in rodents are not relevant to humans.

Species-specific localization of actin in mammalian spermatozoa: fact or artifact?

Actin has been characterized and localized in sperm cells of many mammals. Nevertheless, the reported localizations obtained by different methods and/or antibodies varied from species to species and even for the same species. To clarify the question, sperm actin distribution was reinvestigated under uniform technical conditions. Immunogold post-embedding procedures were performed using a polyclonal and two monoclonal antibodies of known specificity to localize actin in spermatids and spermatozoa of rabbit, mouse, rat, monkey, and human. In these species, actin (F-actin) was detected with the three antibodies between the nucleus and the acrosome of round and elongating spermatids. Species-specific changes occurred in maturing spermatids. In the rabbit, actin labeling decreased and disappeared from the tip to the base of the subacrosomal layer. In testicular and epididymal spermatozoa actin was detected only with a monoclonal antibody (Amersham) successively in the neck, postacrosomal area, and subacrosomal bulges. In mouse late spermatids a transitory labeling of the neck was detected only with the polyclonal antiactin. In testicular and epididymal spermatozoa an actin labeling was observed in the principal piece of the tail. In rat, monkey, and human sperm cells actin remained undetected. These results suggest that there is a redistribution of actin in late spermatids and spermatozoa which is a species-specific process but not an artifact of methodological origin. Thus, a function for actin in sperm, if any, remains to be demonstrated.

Influence of high-dose verapamil on beagle lens proteins (chronic toxicity test).

After oral long-term administration to beagle dogs at doses within toxic and lethal ranges, some animals showed impaired lens transparency. These changes could not be reproduced in rats, even with specifically designed investigations. In man a comparable influence on lens transparency could not be observed either. In the course of further experiments it was demonstrated that the beagle lens changes are a 'species-specific process' which may be attributed to the species-specificity of dog lens proteins. In this study verapamil's influence on the composition of water-soluble and water-insoluble dog lens proteins was tested. 4 beagle dogs were treated daily with a very high dose of 81 mg/kg b.w. verapamil X HCl for 19 months. 3 untreated animals were available as controls. During the mentioned test period microscopic observations with the slit lamp did not reveal any pathological lens findings. In the verapamil-treated animals, however, a lower lens fresh weight and a lower content of water-soluble proteins occurred at the end of the experiment, compared to the control animals of the same age. This indicates a slowing down of lens growth. The distribution of the water-soluble crystallin fractions of dog lenses was determined using thin-layer isoelectric focusing. Significant changes in the single crystallin fractions were demonstrated only in the equator of the lens and in the anterior layer of the cortex. The alpha-crystallin fraction was found to be increased, the beta-crystallin fraction to be decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

A possible model for cell-cell recognition via surface macromolecules

Alternative possibilities for the establishment of the proper cell distribution during embryogenesis are summarized at the beginning, followed by an assessment of the examples known so far where cell-cell recognition is known to be mediated via cell surface components. In the second part the species-specific recognition process which occurs during the sorting-out of dissociated sponge cells is analysed since it may serve as a possible model for cell-cell recognition in higher animals. Three possible mechanisms for the establishment of proper cell distribution are considered. These include, first, chemotaxis: secondly, guidance of cell or cell sheet movement by extracellular matrix or by surrounding cells and thirdly, random movement followed by recognition at the final point of destination. Recognition is necessary for both of the two latter processes, i.e. for cell guidance as well as for locking the cells into their final position after random movement. Two basically different recognition mechanisms should be distinguished from each other. On the one hand cells may recognize each other with the help of macromolecules situated in or just outside of the plasmamembrane which fit to each other like enzymes and substrates or antibodies and antigens. On the other hand, cells may exchange information by exchanging cytoplasmatic components via vesicles or gap junctions. The species-specific aggregation of dissociated sponge cells is considered to be a possible model for cell-cell recognition in higher animals. A proteoglycan-like intercellular macromolecule called aggregation factor seems to mediate recognition of a given species of cells in the reaggregation process of dissociated cells. The data available at the present time suggest that a monovalent surface macromolecule (baseplate) may mediate the recognition process probably by recognizing the carbohydrate side chains of the multivalent proteoglycan aggregation factor. A cell-free system was devised to mimic this aggregation process. Addition of aggregation factor to baseplate-coated sepharose beads of approximately the size of the original sponge cells has essentially the same characteristics as the cellular system. Macromolecule-coded surface information for the recognition between cells has not been established during the embryogenesis of higher animals and remains an interesting challenge.