Pulmonary response, in vivo, to silicon carbide whiskers.

Fischer rats were exposed to silicon carbide whiskers (SiCW), boron carbide whiskers (BCW), silicon carbide platelets (SiCP), or crocidolite asbestos separately administered by intratracheal instillation. SiCW proved to be the most toxic material within the test group. Dramatic increases in alveolar macrophage populations within 1 week of exposure to SiCW persisted for at least 28 days, evidence of the chronic inflammation observed in necropsies during the first months of the study. The most common finding in histological preparations of tissues taken from animals 18 months after exposure to SiCW was a high incidence (frequency > 0.85) of multiple pulmonary granulomas which occasionally occluded airways. Lesions associated with crocidolite were similar to those found with SiCW. Equivalent treatment with BCW and SiCP produced no significant histological changes within 18 months of exposure.

The immediate effects of silicon carbide whiskers upon ciliated tracheal epithelium.

Considering the relationship between toxicity of dust and particle geometry, as exhibited by asbestos, we have examined short-term biological effects of SiC whiskers (SiCW) in vitro and in vivo. Cultured explants of tracheal epithelium were exposed to a range of SiCW concentrations. There were no dramatic effects on ciliary function as measured by an optical spectrum analysis system that provided discrete ciliary frequencies. Particles were swept by ciliary activity into nonciliated regions where foci of extensive cell damage and death were observed with whiskers penetrating epithelial layers into the underlying tissues. Similar necrotic foci were observed in tracheae from rats exposed by intratracheal instillation to SiC whiskers in vivo.

The toxicity, in vitro, of silicon carbide whiskers.

To mouse cells in culture, SiC whiskers (SiCW) and asbestos are similarly cytotoxic, disrupting cell membranes and killing cells. Both shorten cell generation time, increase the rate of DNA synthesis, increase total cell DNA content, and cause a loss in growth control often associated with malignant cellular transformation. Within the narrow size range of materials examined, the amount of damage appeared to be more a function of the number of whiskers present than of their size. Silicon carbide whiskers, if mishandled, may pose a serious health hazard to humans.

Photosensitivity in the skin of the lizard, Anolis carolinensis.

Skin of the lizard, Anolis carolinensis, is remarkably sensitive to light. Illuminated in vitro with visible light from a tungsten source (110 W (m-2)), skin changes from brilliant green to dark brown (50% reduction in reflectance) within 2-4 min as a result of dispersion of melanin from a perinuclear position within dermal melanophores into superficial dendritic processes. Reversal of the process, reaggregation of pigment, will occur within 2.0 min upon return to darkness. This photic response can be initiated with light levels as low as 5.0 W m(-2) and is maximized by light levels only 5% that of midwinter sunshine. Pigment dispersion in response to both melanocyte simulating hormone and to light is inhibited by cytochalasin-B, indicating that microfilaments may be the motor element for pigment movement in that direction. Colchicine, but not cytochalasin-B, totally blocks pigment reaggregation following melanocyte stimulating hormone exposure and partially blocks it in the dark phase of the photic response. The results of this study are consistent with a model for pigment movement in A. carolinensis that provides microfilaments for pigment dispersion and microtubule involvement in both dispersion and aggregation. Finally, because it is readily visible, easily quantified, rapid and reversible, photic response in the skin of A. carolinensis is recommended as a valuable model system for the study of saltatory movement of organelles within cells.

Seasonal changes in oestrogen receptor affinity in the domestic rabbit, Oryctolagus cuniculus.

Over the course of 1 year the Ka value of uterine oestrogen receptor for oestradiol varied 10-fold from a low of 0.259 +/- 0.065 X 10(9) M-1 in early spring to 2.21 +/- 0.21 X 10(9) M-1 in fall. There were no significant changes in receptor number. In addition, administration of oestradiol or progesterone to ovariectomized rabbits resulted in significant reductions in measureable oestrogen receptor affinity. Although these variations in oestrogen receptor Ka values parallel reproductive success in the domestic rabbit, no causal relationship has been established.

Propranolol, a beta-adrenergic antagonist, retards response to MSH in skin of Anolis carolinensis.

Lacking sympathetic innervation, the skin of A. carolinensis, an iguanid lizard, darkens within minutes in response to circulating melanocyte stimulating hormone (MSH) or beta adrenergic agonists such as epinephrine (EPI). This change is produced by dispersion of melanin from a perinculear position within dermal melanophores into superficial dendritic processes. These melanophores possess alpha-2 and beta-2 adrenergic as well as MSH receptors except in a patch of skin behind the eye, the eyespot, which lacks alpha receptors. Activation of beta or MSH receptors leads to stimulation of adenyl cyclase whereas alpha stimulation inhibits the enzyme to override the others. In a series of trials, injection of saline or propranolol was followed after 30 minutes by saline, EPI, or MSH. Propranolol inhibited chromatophore response to EPI. It also, unexpectedly, retarded the response to MSH, increasing latency to eyespot formation and body color change as well as the duration of darkening for both. Alteration of MSH response by a beta blocker could be explained by linkage of both adrenergic receptors and the MSH receptor to a common adenyl cyclase molecule to form a functional unit in the membrane of the melanophore.

The role of adenosine 3',5'-monophosphate in the transformation of Cloudman mouse melanoma cells.

The role of adenosine 3',5'-monophosphate (cyclic AMP) in the regulation of mouse melanoma cell growth and differentiation was investigated. A variant melanoma (Cloudman S91-F) which displays a greater degree of transformation than the parental cell (Cloudman S91) was isolated. A correlation between cyclic AMP metabolism and transformation was made. Dibutyryl cyclic AMP depressed cell growth and increased pigmentation in both parental and variant cell lines. The parental cell line, however, was more responsive to melanocyte-stimulating hormone (MSH) which was found to affect cell growth and pigmentation by increasing cyclic AMP levels. The more transformed S91-F cell line contained lower levels of cyclic AMP than the parental cell line, and this fact correlated well with the higher degree of growth and lesser degree of pigmentation in the variant. Enzymatic analysis revealed that the hydrolysis of cyclic AMP in both cell lines was similar, while the adenylate cyclase activity of the variant cell line was lower than that of the parental cell line. Lineweaver-Burk plots demonstrated that the Km's for the enzymes in the two cell lines were the same but that the Vmax of the S91-F cell line was significantly less that that of the S91 cell line. Thus, the lesion in the S91-F cell which is responsible for its more transformed characteristics seems to be one which affects adenylate cyclase at the level of the cell membrane.

Interaction of two mechanisms regulating alkali cations in HeLa cells.

The alkali cation content of HeLa cells is independent of culture density and of whether the cells are grown in suspension or attached to the culture vessel. With a cell doubling time of 28 hours, the cell K content turns over approximately once per hour. Following partial blockade of the alkali-cation transport system with ouabain, two distinct but interrelated mechanisms operate in the cellular response: (a) an increase in intracellular Na stimulates the pump so that the short-term alteration in electrolyte compostition is less than would be expected from the fraction of pump sites inhibited, and (b) there is a cycloheximide-sensitive recovery in transport capacity reflecting a restoration of functional transport sites to their normal density on the cell surface. Experimental manipulations that mimic the effect of ouabain lead to a stimulation of transport, but they do not result in an increase in the number of ouabain-binding sites on the surface. The data are consistent with a four-to-six hour turn-over of transport sites at the surface, but there is no evidence for a speicific induction of the transport system within this short-term recovery period.

Regeneration of cation-transport capacity in HeLa cell membranes after specific blockade by ouabain.

The cardiac glycoside, ouabain, inhibits alkali-cation transport in HeLa cells. It binds to 0.75 x 10(6) sites per cell, and the half-time for its dissociation is 16 hr. After partial blockade by ouabain, the cell generates new ouabain-binding sites, with total restoration of transport in 10% of a cell cycle( approximately 3 hr). This recovery requires protein synthesis and appears to be a response to altered cell-electrolyte content, since growth of cells in media with low K(+) concentration enhances the titer of the transport enzyme in a fashion similar to the effect of ouabain. Totally blocked cells do not recover.