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Biomedical subjects

V E Reeve

Publications and source records attributed to V E Reeve.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effect of ultraviolet (UV) radiation and UVB-absorbing sunscreen ingredients on 7,12-dimethylbenz(a)anthracene-initiated skin tumorigenesis in hairless mice.

These experiments describe the enhancement of 7,12-dimethylbenz(a)anthracene (DMBA)-initiated skin tumorigenesis in hairless mice by subsequent chronic ultraviolet (UV) irradiation of the same skin site. Each carcinogen was administered at a level that separately resulted in threshold tumorigenesis. The cocarcinogenic response was evident as a marked increase in tumour incidence, tumour multiplicity and degree of tumour malignancy. Irradiation through the topically applied UVB (290-315 nm)-absorbing sunscreen ingredient, 2-ethylhexyl-p-methoxycinnamate, totally protected from the photoenhancement. However, irradiation through an alternative UVB absorber, octyl-N-dimethyl-p-aminobenzoate, failed to protect from photoenhancement. A possible immunologic role for the enhancement of DMBA tumorigenesis by UV radiation is proposed.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Enhancement of u.v.-induced skin carcinogenesis in the hairless mouse by inoculation with cell-free extracts of skin tumours.

The presence of papillomaviral-like DNA has been described in ultraviolet light-induced tumours in the skin of the hairless mouse (14). Here we describe the effects of the inoculation of cell-free extracts of ultraviolet light-induced tumours into the scarified skin of normal hairless mice, prior to exposure of the mice to a cumulative carcinogenic dose of ultraviolet light. Extracts from papillomas or squamous cell carcinomas enhanced the susceptibility of the inoculated mice to ultraviolet light-induced tumorigenesis, if the extracts contained papillomaviral DNA sequences detected by cross-hybridization with Mastomys natalensis papillomaviral DNA. The recipient mice developed a greater tumour incidence, tumour yield, tumour diameter and degree of malignancy.

Animals↗
PubMed1989

Identification of papillomaviral DNA sequences in hairless mouse tumours induced by ultraviolet irradiation.

Papillomas, carcinomas in situ and squamous cell carcinomas were induced using ultraviolet irradiation in the hairless mouse strain Mus musculus HRA/Skh. DNA extracted from biopsies was examined using Mastomys natalensis papillomaviral DNA as a hybridization probe at reduced stringency. Sequences homologous to the probe were detected in 16 of 24 papillomas, five of five carcinomas in situ and six of 38 squamous cell carcinomas. A number of tumour DNAs (16/33) also hybridized with mixed DNAs of human papillomavirus types 11, 13, 16 and 18 at reduced stringency. This suggests a role for the hairless mouse as a laboratory model for the study of the involvement of papillomaviruses in malignant transformations.

Animals↗
PubMed1989

Topical urocanic acid enhances UV-induced tumour yield and malignancy in the hairless mouse.

Epidermal urocanic acid has been postulated to be the mediator of the specific state of immunosuppression induced by UV irradiation, by which UV-initiated tumour cells are able to evade normal recognition and can survive to grow progressively into malignant tumours. These experiments demonstrate that topical application of UV-irradiated urocanic acid systemically suppresses the contact type hypersensitivity response to oxazolone in hairless mice. In addition, topically applied urocanic acid markedly increases the overt tumour yield and the degree of malignancy in hairless mice exposed chronically to daily minimally erythemal doses of simulated solar UV light. Topical urocanic acid also increases the number of latent UV-initiated tumours, detectable by croton oil promotion. Therefore UV photoproducts of urocanic acid can both systemically suppress contact hypersensitivity in the epidermis, and also enhance early survival of UV-initiated tumour cells resulting in augmentation of UV photocarcinogenesis.

Animals↗
PubMed1988

The characterization of squamous cell carcinoma induced by ultraviolet irradiation in hairless mice.

Squamous cell carcinomas (SCCs) induced by ultraviolet irradiation in hairless mice were characterized according to their growth, gross appearance and light and transmission electron microscopic features. SCCs arose directly from irradiated skin (ab initio) or progressed from pre-existing epidermal tumours and lesions. SCCs could be graded using guidelines established for human tumours. SCCs comprised 60.8% of the tumours examined. Of these, 35.6% were designated as grade 1, 27.7% as grade 2, 7.9% as grade 3 and 28.7% as grade 4. Spindle cell tumours suspected of being SCCs were included in grade 4. Grades 1, 2 and 3 could not be distinguished on the basis of growth and gross appearance. Those arising ab initio presented as either red, ulcerated lesions or as raised, white, verrucose lesions. Grade 4 SCCs that arose ab initio presented as rapidly growing, red, spherical lesions. Those that arose from pre-existing tumours or lesions had no characteristic appearance, and variable growth. Light microscopically, grade 4 SCCs with an obvious point of origin from epidermis or other epidermal tumours, and putative grade 4 SCCs without such a point of origin, were characterized commonly by spindle cells, pleomorphic giant or multinucleated cells and individual cell reticular fibres. Ultrastructurally, spindle cells, although poorly differentiated, were distinct from flibroblastic proliferations and had few tonofilaments or desmosomes, and were inconsistently surrounded by basal lamina-like material. On the basis of these characteristics, and despite inconclusive positivity with immunoperoxidase staining for keratin and prekeratin, it was concluded that these spindle cell tumours were most probably of identical squamous cell origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Ultrastructure of ultraviolet radiation-induced hairless mouse skin carcinogenesis, with special reference to the epidermal-dermal junction.

The ultrastructure of ultraviolet (UV)-induced skin pathology was studied in mice to complement previously reported gross and light microscopic findings, and to assess further the usefulness of the animal model for study of sunlight associated epidermal tumours in man. Hairless albino (HRA/Skh-1) mice were exposed to a minimal erythemal dose from a filtered light source emitting both UVA and UVB, approximating solar emission. Samples of normal and hyperplastic skin, pedunculated papillomas, carcinomas in situ and invasive squamous cell carcinomas were processed for transmission electron microscopy once their identity was confirmed by light microscopic examination. Keratinocyte pleomorphism became more marked and cell to cell contact diminished as malignancy developed. For papillomas, carcinomas in situ and invasive squamous cell carcinomas, there was a progressive disruption of the epidermal junction which became marked upon frank invasion. Most of the differences between the various categories of pathological change, therefore, were not absolute but rather of degree, supporting the notion that invasive squamous cell carcinoma represents an end stage for malignancy which may arise de novo, directly from hyperplastic skin, or proceed from other tumour types. The similarity in structure of the mouse tumours to comparable tumours in man supports the usefulness of the animal model and suggests that the results have implications for sunlight associated tumours in man.

Animals↗
PubMed1985

Effect of immunosuppressive agents and sunscreens on UV carcinogenesis in the hairless mouse.

The effect of two immunosuppressive agents, azathioprine and cyclophosphamide, with and without UVB sunscreen protection on UV-induced skin carcinogenesis was studied in the albino hairless mouse. In a daily treatment regime spanning 9 weeks, groups of mice were immunosuppressed with either drug, and were exposed to minimally erythemal doses of a light source simulating the UV portion of the solar spectrum. The accumulated UV exposure alone induced skin tumours in 77% of mice. Azathioprine, but not cyclophosphamide, significantly enhanced the incidence of UV tumorigenesis. Photoprotection by topical application of one of two commonly used UVB sunscreens, 2-ethyl-hexyl-p-methoxycinnamate (2-EHMC) or octyl-N-dimethyl-p-aminobenzoate (o-PABA), reduced the UV tumour incidence to zero in immunologically normal mice and to 8-15% in immunosuppressed mice. Unexpressed latent tumour initiations were revealed in all sunscreen-protected groups by the subsequent application of a tumour promoter, croton oil. In immunologically normal mice 2-EHMC had allowed initiations in 39% of UV-irradiated mice, and o-PABA in 16.5%. However, in UV-irradiated mice immunosuppressed with azathioprine there had been initiations in 78% of mice protected with 2-EHMC and 65% of mice protected with o-PABA. Photoprotected mice immunosuppressed with cyclophosphamide did not show the same increase in UV-initiations (22% with 2-EHMC, 23% with o-PABA). These results provide evidence that azathioprine increases the susceptibility of the skin to UV carcinogenesis. However, UVB sunscreens afford effective protection from overt tumour expression in the absence of a tumour promoter.

4-Aminobenzoic Acid↗
PubMed1985

Characterization of UV induced keratoacanthoma-like lesions in HRA/Skh-1 mice and their comparison with keratoacanthomas in man.

UV induced keratoacanthoma-like lesions in mice were studied grossly, light microscopically and electron microscopically. The tumours varied in their degree of cell organization and keratinization but all exhibited downward growth and had a continuous basement membrane. Ultrastructurally, the keratinocytes displayed villous distortion of their plasma membranes, and at times the basal lamina of the epidermal-dermal junction showed focal discontinuation. The keratoacanthoma-like lesions in mice had similarities of appearance to keratoacanthoma in man but showed no regression and regularly progressed to squamous cell carcinoma. This clinical course is dissimilar to that of keratoacanthoma in man which suggests that the use of the term is inappropriate for these UV induced tumours. Moreover, in the context of our experimental system and a dynamic picture of tumour development where tumour types can be seen as stably arising and continuing entities or, a progressive sequence for which squamous cell carcinoma represents an end stage, it is not appropriate to view the keratoacanthoma-like lesion in mice as an entity distinct from the spectrum of UV induced tumours progressing from benignity to malignancy.

Animals↗
PubMed1985

Bovine post-parturient haemoglobinuria: effect of inorganic phosphate on red cell metabolism.

Washed red blood cells from normal cows were incubated as 10 and 20 per cent suspensions in media containing 0, 2.5 and 25 mM phosphate. The results showed that the rate of glycolysis was dependent on the inorganic phosphate concentration. In the absence of phosphate, the consumption of glucose and the production of 2,3-diphosphoglycerate, lactate and adenosine 5'-triphosphate (ATP) were decreased. Incubation without added phosphate also greatly increased the production of fructose-1,6-diphosphate, glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Moderate hypophosphataemia was induced in two pre-ruminant calves. Washed red cells from the blood of these animals showed a depletion of ATP when compared with red cells from a control calf. The results indicate that phosphorus deficiency, leading to hypophosphataemia, may be a mechanism of post parturient and related syndromes of haemoglobinuria by decreasing red cell glycolysis and resultant ATP synthesis. Subnormal concentrations of ATP would predispose red cells to altered structure and function, a loss of normal deformability, and an increase in fragility and haemolysis with resultant haemoglobinuria.

Adenosine Triphosphate↗
PubMed1984

Ultraviolet carcinogenesis in the hairless mouse skin. Influence of the sunscreen 2-ethylhexyl-p-methoxycinnamate.

The mutagenicity of some samples of a commonly used sunscreen, 2-ethylhexyl-p-methoxycinnamate (2-EHMC), led to these studies of its potential carcinogenicity in the HRA/Skh hairless mouse. In a daily treatment regime, repeated for 9 weeks, groups of mice were painted on the dorsum with 2-EHMC, and were then exposed to low doses of one of two artificial ultraviolet (UV) light sources. Mice were also treated with UV alone and with 2-EHMC alone. The accumulated UV exposure alone produced tumours in 40-100% of mice. However, 2-EHMC-treated mice were protected. Subsequent treatment of the 2-EHMC-protected mice, and mice previously treated with 2-EHMC alone, with the tumour promoter, croton oil, produced tumours on a significant number of animals. We conclude that 2-EHMC protects from UV tumorigenesis in the absence of a tumour promoter. However, although tumours appeared on only 4 out of 160 2-EHMC-treated mice exposed to UV, the carcinogenic process had been initiated in others, as application of the tumour promoter, croton oil, produced tumours. Statistical analysis of the incidence of promoted tumours inferred that prior irradiation with UV may not have been implicated. Therefore, 2-EHMC itself may initiate tumours in this strain of hairless mouse.

Animals↗
PubMed1984

Characterization and histogenesis of tumors in the hairless mouse produced by low-dosage incremental ultraviolet radiation.

Tumors were induced in the HRA/Skh-1 hairless mouse by repeated irradiations of minimally erythemal and suberythemal doses of UV radiation. Aspects of tumor induction were recorded using a combined system of mapping and gross descriptive classification. Tumors of epithelial and dermal (mesenchymal) origin were confirmed histologically and their types correlated well with those reported by earlier investigators. Among those classified, however, appendage tumors and hemangiomas have rarely been described. The progression to malignancy of epithelial tumors was systematically characterized and was a consistent histogenic feature in our experiments. Squamous cell carcinomas represented a final stage for development arising ab initio or from other forms, in particular papillomas which commonly passed through intermediate forms toward definite malignancy. While confirming previous studies of UV-induced tumors, this report extends our knowledge of their dynamics as this bears upon any experimental objective which includes an assessment of tumorigenicity.

Animals↗
PubMed1982

Influence of coenzyme A on the in vitro binding of benzo(a)pyrene metabolites to protein.

Incubation of 20,000 xg supernatants of liver homogenates from female Wistar rats with benzo(a)pyrene (BP) and other cofactors in the presence of coenzyme A (CoA) produced metabolites that required extensive hydrolysis successively in 2N NaOH, 2N HCl, 2N NaOH and 6N HCl for their release. It is suggested that coenzyme A activated benzpyrenyl-amino acid formed via epoxide(s). The activated amino acid(s) became bound to thiol protein.

Animals↗
PubMed1981

Metabolism of [14C]benzo[a]pyrene in vivo in the rat.

[14C]Benzo[a]pyrene ([14C]B[a]P) injected intraperitoneally into rats appeared rapidly in liver, lung and kidney, and remained detectable in these tissues for at least 7 days. A large proportion (7--13%) of the 14 C became covalently bound to tissue macromolecules, probably primarily proteins. Subcellular organelles of the liver were all found to bind the carcinogen, the microsomes most rapidly and the light mitochondrial fraction taking up 14C later. Nuclear bound 14C was detected in both liver and lung. Purification of the cytosolic 14C from liver revealed specific binding to the same cytosolic proteins purified from the in vitro reaction of [14C] B[a]P.

Animals↗
PubMed1976

Interrelationships of copper, cytochrome oxidase, phospholipid synthesis and adenine nucleotide binding.

Studies are reported on the interrelationships in liver mitochondria of copper status, cytochrome oxidase activity, adenine nucleotide binding capacity and phospholipid synthesis. Direct exposure of mitochondria to cyanide or diethyldithiocarbamate depressed cytochrome oxidase activity; ADP-binding and phospholipid synthesis. Fractionation of mitochondria to increase the specific activity of cytochrome oxidase about 10-fold did not increase the affinity to bind ADP. Ageing of mitochondria or dialysis of mitochondria or mitochondrial membrane preparations against water or diethyldithiocarbamate at 0--2 degrees for 18 h did not decrease cytochrome oxidase activity or copper content of reisolated and resuspended mitochondria or mitochondrial membrane preparations, but considerably reduced the affinity to bind ADP. The respiratory inhibitors, fluoride and azide, at concentrations inhibitory to cytochrome oxidase did not reduce ADP-binding or phospholipid synthesis. Atractyloside did not inhibit cytochrome oxidase activity but did inhibit ADP-binding and phospholipid synthesis. Pre-incubation of mitochondrial membrane preparations with Cu++ increased the copper content and ADP-binding affinity. The results indicate that cytochrome oxidase is not the ADP-binding site of the mitochondrial membrane system and that reduced cytochrome oxidase activity per se does not depress binding affinity. Copper appears to be a component of the adenine nucleotide binding sites of mitochondrial membranes because the copper-complexing agents, cyanide and diethyldithiocarbamate, depressed ADP-binding, while increased mitochondrial membrane copper content increased ADP-binding.

Adenosine Diphosphate↗
PubMed1976

Coppr deficiency in the rat. Relationship to chronic cyanide poisoning.

Daily administration of increasing doses intraperitoneally of 2.5-4.0 mg NaCN/kg to male Wistar rats for 5 weeks produced acute signs of poisoning immediately post-injection but no sign of chronic toxicity except lower final body weights than in control rats. CN-treated rats had less liver copper than controls, but not below the range of normality, and their liver mitochondrial membranes were 24% less able to bind adenine nucleotides than control membranes. No other biochemical or pathological sign of copper deficiency occurred. Liver cytochrome oxidase activity was normal after the 5 weeks of CN-administration, as was the ability of liver mitochondria to synthesize phospholipids. The ultrastructure of hepatocytes was normal without evidence of the enlarged, misshapen mitochondria produced by copper deficiency. Normal cytochrome oxidase activity of liver mitochondria, together with reduced liver copper levels and reduced binding affinity of mitochondrial membranes for adenine nucleotides, indicate that the membrane binding site for adenine nucleotides is not cytochrome oxidase per se but may involve copper, perhaps by virtue of its cationicity. With repeated exposure to CN- rats develop tolerance to acute poisoning. It is suggested that this may be due to the switch in glucose catabolism towards the pentose pathway at the expense of other pathways.

Adenosine Diphosphate↗