Alterations in cell-cell interactions induced by urea and urea-isolated cell-surface protein (CSP) were examined using the nontumorigenic mouse fibroblast 10T1/2 cell line and the malignantly transformed MCA daughter cell line as a model system. Both cell lines were exposed to urea and CSP, and contact inhibition was quantitated based on nuclear overlaps. The Abercrombie Overlap index was found to be dependent on cell density, and a new method of overlap analysis was developed based on the regression of the number of overlaps per microscope field on the number of cells per field. Urea had a differential effect on both protein and deoxyribonucleic acid synthesis and a differential effect on the overlap regression in the two cell lines. Urea increased the regression coefficient in the normal (10T1/2) cell line while decreasing it in the transformed (MCA) cell line to approximately equal levels of overlap. Added CSP had no effects on overlaps in the MCA line but increased overlaps in the 10T1/2 line to the level of the MCA control, suggesting that the CSP interactions were more specific than the urea interactions. Trypsin-derived cell-surface glycopeptide profiles of the two cell lines showed a difference consistent with previously reported differences between normal and transformed cell lines. However, the glycopeptide profile of the urea-isolated CSP from the normal 10T1/2 cell line and the trypsin-derived glycopeptides of the transformed MCA cell line were not significantly different in the high-molecular-weight region, suggesting that the relative abundance of CSP may be higher in the MCA line, and the fact that the addition of CSP to the 10T1/2 line increased overlap tendency to the level of the MCA line suggested that CSP is an important factor in the modulation of overlap tendency. Urea and CSP may exert their effects on overlap tendency by affecting the integrity or order of the cell-surface components. The increased overlap tendency of the 10T1/2 line in the presence of CSP was not associated with increased cell density. Density dependence of cell growth was apparently not directly related to density dependence of overlap tendency. Many xenobiotics have surface-active properties and are known to inhibit protein synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

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Impaired metabolism of di(2-ethylhexyl) phthalate (DEHP) in old rats--an in vitro study.

Liver, kidney, and lung homogenates from 45- and 630-d-old rats were incubated with 0.5 muCi of 14C-labeled di(2-ethylhexyl) phthalate (DEHP) for 40 min at 37 degrees C. Radiochromatogram scans of the ether extracts of the incubated mixtures showed the presence of a peak corresponding to the hydrolytic product monoethylhexyl phthalate (MEHP), in addition to the parent DEHP. Preparations from old animals revealed another radioactive zone along with MEHP. A dramatic reduction in the formation of MEHP was observed only with homogenates of livers from the old animals. It is shown that this difference is probably attributable to differences in Km values of the enzymes from adult and old rats respectively. Protein content in the three tissues did not differ between young and old animals. Formation of MEHP is a major step in the metabolic pathway of the plasticizer DEHP. Impairment of this conversion could possibly alter the rate of its excretion and hence its toxicologic significance.

Age Factors↗

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