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Biomedical subjects

J E Strickland

Publications and source records attributed to J E Strickland.

13 recordsLinked to original sources

A model for initiated mouse skin: suppression of papilloma but not carcinoma formation by normal epidermal cells in grafts on athymic nude mice.

The availability of a skin grafting system on nude mouse hosts and of epidermal cell lines which form papillomas when grafted has made possible the creation of a model for initiated skin in vivo from cultured cells. When grafted with 6-8 x 10(6) primary dermal fibroblasts, 10 x 10(6) primary epidermal cells form an apparently normal skin, and cell line SP-1 (0.5 x 10(6) cells) forms papillomas. Cell line SP-1 was derived from papillomas produced on SENCAR mice by initiation with 7,12-dimethylbenzaadaa]anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate. Grafting of 0.5 x 10(6) SP-1 cells along with 10 x 10(6) SENCAR newborn primary epidermal cells resulted in a 90% reduction in the average papilloma volume per mouse compared to controls without primary epidermal cells. Suppression occurred specifically with epidermal cells, either cultured or freshly prepared, and was not seen when an equivalent number of SENCAR primary dermal fibroblasts was grafted in place of epidermal cells. Nor did suppression occur when primary epidermal cells were replaced with a carcinogen-altered cell line, SCR722. SCR722 cells have a normal-skin phenotype when grafted. Furthermore, suppression of tumor formation did not occur when a malignant variant of SP-1 cells replaced benign SP-1 cells in grafts. Repeated treatment of suppressed grafts with 12-O-tetradecanoylphorbol-13-acetate resulted in an increased number of mice with papillomas and a larger mean papilloma volume per mouse compared to controls treated with solvent alone, whereas treatment of nonsuppressed grafts of papilloma cells with promoter produced no change in tumor size. These results support the concepts that normal epidermal cells suppress the growth of initiated cells and that repeated treatment with phorbol ester tumor promoters overcomes the suppression, leading to benign tumor formation.

9,10-Dimethyl-1,2-benzanthracene

v-Ha-ras-induced mouse skin papillomas exhibit aberrant expression of keratin K13 as do their 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate -induced analogues.

Introduction of the v-Ha-ras gene into primary epidermal keratinocytes, followed by grafting of these cells to animals, leads to the formation of benign epidermal tumors that resemble papillomas induced chemically by a two-stage carcinogenesis protocol. In this study, we investigated v-Ha-ras-induced papillomas for aberrant expression of type I keratin K13, previously described in 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13- acetate (DMBA/TPA)-induced mouse epidermal tumors. Papillomas produced from three independent infection series were removed 3 wk after grafting concomitant with control grafts originating from mock-, neo-, and v-fos-infected primary keratinocytes. Combined analysis of the grafts by western blotting of extracted keratins and immunofluorescence studies of frozen sections with a K13-monospecific antibody revealed K13 expression in all v-Ha-ras-induced papillomas and absence of this keratin in all control grafts. K13-positive cells in papillomas were restricted to the suprabasal cell layers of the lesions and, at this stage of papilloma development, occurred as foci of varying extensions. Analysis of genomic DNA from v-Ha-ras-induced papillomas for the methylation state of a CpG dinucleotide in the distant promoter region of the K13 gene revealed the occurrence of unmethylated DNA copies that were generated at the expense of methylated DNA copies ubiquitously present in normal epidermis. The ratio of unmethylated to methylated DNA copies correlated with the extent of suprabasal K13 protein expression. Thus, all features of aberrant K13 expression previously described in DMBA/TPA-induced papillomas were shared by v-Ha-ras-induced papillomas.

9,10-Dimethyl-1,2-benzanthracene

Suprresion of in vitro lymphocyte stimulation in mice by uterine and placental extracts.

The effects of uterine extracts from virgin mice and uterine and placental extracts from mice at various stages of gestation on lymphocyte stimulation in vitro were compared. Placental and uterine extracts from mice in gestation, at 1% final concentration by volume, caused marked depression of lymphocyte reactivity to phytohemagglutinin-P (PHA) and to allogeneic cells in two-way mixed leukocyte cultures (MLC). An equivalent concentration of uterine extract from virgin mice caused slight depression of uterine extract from virgin mice caused slight depression of lymphocyte reactivity. Suppression was most of lymphocyte reactivity. Suppression was most marked with uterine extracts of mice at 15 days of gestation. At least two factors of different m.w. in uterine and placental extracts were responsible for suppression of lymphocyte reactivity. The higher m.w. fraction, present in small amounts in the uteri of virgin mice, was markedly increased in uteri of pregnant mice. This fraction contained immunoglobulin G (IgG). These factors may be involved in a protective role for the fetus from rejection by the mother as an allograft, thus assuring successful pregnancy.

Animals

A comparative study on the presence of C-type viral particles in placentas from primates and other animals.

C-type particles are found in human, baboon, marmoset, rhesus, patas, and cynomolgus monkeys. A cebus monkey and two chimpanzee placentas have failed thus far to show the presence of these particles. Of the nonprimate tissues examined one mouse and one guinea pig placenta were positive whereas a rabbit placenta was negative. Variations in number of particles present in tissues as well as number of animals of a given species containing particles are noted. The isolation of foamyviruses from placenta cultures makes critical evaluation and interpretation of findings imperative. Several considerations suggest that the presence of foamyviruses is coincidental.

Animals

Oncornaviral protein modulation in mouse uterine tissue by estrogen (38467).

Treatment of ovariectomized NIH Swiss mice with estrogens elevated the level of the murine leukemia virus group specific protein and the activity of an RNA-directed DNA polymerase in the uterus. The extent that these markers were raised was dependent on the relative biological potency of the estrogen and on the time interval following treatment. Increases in the levels of both viral marker proteins were evident within 24 hr of treatment and were highest at 48 hr. Subsequently, viral protein levels declined to pretreatment levels.

Animals