Biomedical subjects

V E Reeve

Publications and source records attributed to V E Reeve.

At least 37 records · Page 2Linked to original sources

PubMed1997

Cis-urocanic-acid-induced suppression of contact hypersensitivity in Monodelphis domestica is prevented by ultraviolet A radiation/photoreactivating light.

The suppression of contact hypersensitivity by UVB (280-320 nm) radiation can be prevented by photoreactivating light (PRL; 320-400 nm) in the opossum Monodelphis domestica, implicating epidermal DNA lesions as the immunosuppressive impairment. However, contact hypersensitivity can also be suppressed in the opossum with exogenous cis-urocanic acid, a molecule which is produced in UVB-irradiated epidermis and is a second potential mediator of photo-immunosuppression apparently independent of UVB-induced DNA damage. Here we demonstrate that irradiation of opossums with PRL either before or following treatment with exogenous cis-urocanic acid, significantly reduced the degree of immunosuppression. This suggests that, in addition to its capacity to initiate post-UVB-exposure epidermal DNA repair, the PRL waveband can induce an immunoprotective product, as yet unidentified, in opossum epidermis.

Administration, Topical↗

PubMed1997

Chemoprevention of ultraviolet radiation-induced skin cancer.

The use of chemical and physical sunscreening agents has increased dramatically during the last two to three decades as an effective means of preventing sunbum. The use of high sunprotection factor sunscreens has also been widely promoted for the prevention of skin cancer, including melanoma. Whereas sunscreens are undoubtedly effective in preventing sunbum, their efficacy in preventing skin cancer, especially melanoma, is currently under considerable debate. Sunscreens have been shown to prevent the induction of DNA damage that presumably results from the direct effects of ultraviolet radiation (UVR) on DNA. DNA damage has been identified as an initiator of skin cancer formation. However, both laboratory and epidemiological studies indicate that sunscreens may not block the initiation or promotion of melanoma formation. These studies suggest that the action spectrum for erythema induction is different than the action spectrum for the induction of melanoma. Indeed, recent reports on the wavelength dependency for the induction of melanoma in a fish model indicate that the efficacy of ultraviolet A wavelengths (320-400 nm) to induce melanoma is orders of magnitude higher than would be predicted from the induction of erythema in man or nonmelanoma skin tumors in mice. Other strategies for the chemoprevention of skin cancer have also been reported. Low levels and degree of unsaturation of dietary fats protect against UVR-induced skin cancer in mice humens. Compounds with antioxidant activity, including green tea extracts (polyphenols), have been reported to inhibit UVR-induced skin carcinogenesis.

Antioxidants↗

PubMed1996

Dependence of photocarcinogenesis and photoimmunosuppression in the hairless mouse on dietary polyunsaturated fat.

A series of semi-purified diets containing 20% fat by weight, of increasing proportions (0, 5%, 10%, 15% or 20%) of polyunsaturated sunflower oil mixed with hydrogenated saturated cottonseed oil, was fed to groups of Skh:HR-1 hairless mice during induction and promotion of photocarcinogenesis. The photocarcinogenic response was of increasing severity as the polyunsaturated content of the mixed dietary fat was increased, whether measured as tumour incidence, tumour multiplicity, progression of benign tumours to squamous cell carcinoma, or reduced survival. At the termination of the study approximately 6 months following the completion of the 10-week chronic UV irradiation treatment, when most mice bore tumours, the contact hypersensitivity (CHS) reactions in those groups supporting the highest tumour leads (fed 15% or 20% polyunsaturated fat), were significantly suppressed in comparison with the mice bearing smaller tumour loads (fed 0, 5% or 10% polyunsaturated fat). When mice were exposed acutely to UV radiation (UVR), a diet of 20% saturated fat provided almost complete protection from the suppression of CHS, whereas feeding 20% polyunsaturated fat resulted in 57% suppression; the CHS of unirradiated mice was unaffected by the nature of the dietary fat. These results suggest that the enhancement of photocarcinogenesis by the dietary polyunsaturated fat component is mediated by an induced predisposition to persistent immunosuppression caused by the chronic UV irradiation, and supports the evidence for an immunological role in dietary fat modulation of photocarcinogenesis in mice.

Animals↗

PubMed1996

Dietary butter protects against ultraviolet radiation-induced suppression of contact hypersensitivity in Skh:HR-1 hairless mice.

Dietary fats modulate a wide variety of T cell functions in mice and humans. This study examined the effects of four different dietary fats, predominantly polyunsaturated sunflower oil, margarine, and predominantly saturated butter, clarified butter, on the T cell-mediated, systemic suppression of contact hypersensitivity by ultraviolet radiation in the Skh:HR-1 hairless mouse. Diets containing either 200 g/kg or 50 g/kg butter or clarified butter as the sole fat source protected against systemic photoimmunosuppression, whether the radiation source was unfiltered ultraviolet B (280-320 nm) or filtered solar simulated ultraviolet radiation (290-400 nm), in comparison with diets containing either 200 or 50 g/kg margarine or sunflower oil. There was a linear relationship (r > 0.9) between protection against photoimmunosuppression and the proportion of clarified butter in mice fed a series of 200 g/kg mixed fat diets that provided varying proportions of clarified butter and sunflower oil. The dietary fats did not modulate the contact hypersensitivity reaction in unirradiated animals. The observed phenomena were not primary due to the carotene, tocopherol, cholecalciferol, retinol, lipid hydroperoxide or the nonfat solid content of the dietary fats used and appeared to be a result of the different fatty acid composition of the fats.

Animals↗

PubMed1996

Epidermal urocanic acid and suppression of contact hypersensitivity by ultraviolet radiation in Monodelphis domestica.

A single specific epidermal photoreceptor for the immunosuppressive action of UV radiation has not been defined, although separate evidence is accruing in favour of each of two candidates, trans-urocanic acid and DNA. In Monodelphis domestica, specific photoreactivation repair of UV radiation-induced pyrimidine dimers has been shown to abrogate the suppression of contact hypersensitivity (CHS), thus suggesting that DNA is the target for this impairment. However, the both haired and hairless mice, immunosuppressive effects of UV radiation have been reproduced by the exogenous administration of the UV photoproduct of urocanic acid, cis-urocanic acid. We show here that the epidermis of M. domestica contains urocanic acid, that UV irradiation of the shaved dorsal skin has resulted in an increase in epidermal cis-urocanic acid and that the topical application of a cis-urocanic acid-containing lotion significantly depressed the capacity of Monodelphis to respond to contact sensitisers, in a manner analogous to these responses in the hairless mouse. Therefore in Monodelphis, suppression of CHS by UV irradiation appears to involve both urocanic acid photo-isomerisation and epidermal DNA damage.

Administration, Topical↗

PubMed1995

The protective effect of indomethacin on photocarcinogenesis in hairless mice.

Orally administered indomethacin at 10-600 micrograms per mouse per day has been shown to inhibit UV radiation-induced erythema dose responsively. At the higher doses tested (200-600 micrograms) there was evidence of drug toxicity. Indomethacin administered orally at 20 micrograms per mouse daily during photocarcinogenesis induction both increased the probability of remaining tumour free and reduced the average tumour multiplicity. When indomethacin was administered only during the UV irradiation period (initiation), a reduction in tumour multiplicity and in the progression of tumours to malignant squamous cell carcinomas was observed; when administered only during the post-irradiation promotion period, there was a significant increase in the probability of remaining tumour free. Thus both tumour initiation and promotion by UV radiation appear to be indomethacin-sensitive, possibly affected by different mechanisms.

Animals↗

PubMed1995

Pyridoxine supplementation protects mice from suppression of contact hypersensitivity induced by 2-acetyl-4-tetrahydroxybutylimidazole (THI), ultraviolet B radiation (280-320 nm), or cis-urocanic acid.

Evidence exists implicating the epidermal ultraviolet B (UVB) photoproduct cis-urocanic acid as an immunogenic mediator of the systemic suppression of T cell-mediated immunity by UVB exposure. Cis-urocanic acid appears to act via histamine receptor pathways, and histamine receptor antagonists and other imidazole ring compounds may modify its immune suppressing action. A component of the food coloring substance ammonia caramel, 2-acetyl-4-tetrahydroxybutylimidazole (THI), which is known to cause lymphopenia in rats, appears to suppress immunity by a similar pathway when the contact hypersensitivity reaction has been the immune function assay in mice. The induction of lymphopenia in rats by THI is inhibited by the vitamin pyridoxine. This study demonstrates that the suppression of contact hypersensitivity in mice by UVB radiation, cis-urocanic acid, or THI is strongly inhibited by supplemental pyridoxine, fed at 30 mg/kg diet, in comparison with the normal diet, which supplies 7 mg pyridoxine/kg diet. These results suggest that pyridoxine competes with cis-urocanic acid and THI for the same binding site or receptor, which we postulate to be a histamine-like T lymphocyte receptor, and that a role may exist for the control of photoimmunosuppression by this vitamin.

Animals↗

PubMed1994

Differential photoimmunoprotection by sunscreen ingredients is unrelated to epidermal cis urocanic acid formation in hairless mice.

A series of experimental sunscreen preparations based on a common vehicle, containing increasing concentrations of either octyl-N-dimethyl-p-aminobenzoate (o-PABA) or 2-ethylhexyl-p-methoxycinnamate (2-EHMC) as the ultraviolet B (UVB) absorber, has been tested in the hairless mouse for the ability to protect from erythema, from the systemically suppressive effects of UVB (280-320 nm) radiation on contact hypersensitivity, and from photoisomerization of epidermal urocanic acid. All the preparations protected efficiently from the edema component of the erythema response when mice were exposed to UVB radiation equivalent to three times the minimal erythema dose (MED). However, when mice were exposed to UVB radiation equivalent to 15 x MED, protection from erythema was observed only at the higher concentrations of each UVB absorber (10% 2-EHMC and 10% or 15% o-PABA). Protection from the UVB-induced suppression of contact hypersensitivity was shown to be dependent on both the nature of the UVB absorber and its concentration. Photoimmunoprotection by the sunscreens containing 2-EHMC was evident at lower concentrations (5% and 10% 2-EHMC) than with o-PABA, following both 3 x MED and 15 x MED of UVB exposure. Photoimmunoprotection by o-PABA-containing sunscreens was observed only at 15% o-PABA following 3 x MED, and failed at all tested concentrations after 15 x MED of UVB exposure. Regardless of the photoimmunoprotective capacity, sunscreen preparations containing either of the UVB absorbers prevented the UVB-induced formation of cis urocanic acid in the mouse epidermis and in vitro under all conditions tested. Thus, there appeared to be a correlation between protection from edema and from cis urocanic acid formation at 3 x MED of UVB, but a dissociation of these variables at 15 x MED of UVB. There was no relation apparent at either UVB dose between either edema or cis urocanic acid formation and protection from suppression of contact hypersensitivity.

4-Aminobenzoic Acid↗

PubMed1994

Lack of correlation between suppression of contact hypersensitivity by UV radiation and photoisomerization of epidermal urocanic acid in the hairless mouse.

The immunological consequences of exposure to UVA (320-400 nm) radiation are unclear. This study describes the relationship between the generation of epidermal cis-urocanic acid and the ability to respond to a contact-sensitizing agent, in hairless mice exposed to different UV radiation sources, which incorporate successively greater short-wavelength cutoff by filtration of the radiation from fluorescent UV tubes. Mice were exposed to these radiation sources at doses systematically varying in UVB radiation content but supplying increasing proportions of UVA radiation. All radiation sources were found to generate approximately 35% cis-urocanic acid in the epidermis, thus normalizing the sources for cis-urocanic acid production. However, only those sources richest in short-wavelength UVB resulted in suppression of the systemic contact hypersensitivity response. These sources also induced the greatest erythema reaction, measured as its edema component, in the exposed skin. A strong correlation was thus demonstrated between the induction of edema and the suppression of contact hypersensitivity, but there appeared to be no correlation between the generation of epidermal cis-urocanic acid and suppression of contact hypersensitivity. The sources richest in UVA content did not result in suppression of contact hypersensitivity; furthermore mice previously irradiated with such UVA-rich sources were refractory to the immunosuppressive action of exogenous cis-urocanic acid. A protective effect of the increased UVA content thus appeared to be inhibiting immunosuppression by the available endogenously generated or exogenously applied cis-urocanic acid.

Animals↗

PubMed1993

A garlic extract protects from ultraviolet B (280-320 nm) radiation-induced suppression of contact hypersensitivity.

Lyophilized aged garlic extract has been incorporated at concentrations of 0.1%, 1% and 4% by weight into semipurified powdered diets and fed to hairless mice. Under moderate UVB exposure conditions resulting in 58% suppression of the systemic contact hypersensitivity response in control-fed mice, a dose-responsive protection was observed in the garlic-fed mice; contact hypersensitivity in the UVB-exposed mice fed 4% garlic extract was suppressed by only 19%. If the UVB exposure was replaced by topical application of one of a series of lotions containing increasing concentrations of cis-urocanic acid, a dose-responsive suppression of contact hypersensitivity was demonstrated in control-fed mice (urocanic acid at 25, 50, 100 and 200 micrograms per mouse resulting in 22-46% suppression). Mice fed a diet containing 1% aged garlic extract were partially protected from cis-urocanic acid-induced suppression of contact hypersensitivity, with greater protection from the lower concentrations of urocanic acid. Mice fed a diet containing 4% aged garlic extract were protected from all concentrations of urocanic acid. The results indicate that aged garlic extract contains ingredient(s) that protect from UVB-induced suppression of contact hypersensitivity and suggest that the mechanism of protection is by antagonism of the cis-urocanic acid mediation of this form of immunosuppression.

Administration, Oral↗

PubMed1993

Suppressive effect of 2-acetyl-4-tetrahydroxybutylimidazole on contact hypersensitivity in the Skh: HR hairless mouse.

The compound 2-acetyl-4-tetrahydroxybutylimidazole (THI), a component of ammonia caramel, has been shown to cause lymphopenia and to impair several immune functions in rats and mice. In this study we show that THI effectively suppresses contact hypersensitivity dose responsively in the hairless mouse, whether administered topically or orally. The suppression was shown to be prevented by topical administration of the histamine antagonist, cimetidine, and by the dipeptide, carnosine. Splenocytes from THI-treated mice failed to elicit normal contact hypersensitivity when transferred to naive mice. This suggests that THI acts by modifying splenocyte function, perhaps via a histamine-like receptor site(s).

Administration, Oral↗

PubMed1993

Carnosine (beta-alanylhistidine) protects from the suppression of contact hypersensitivity by ultraviolet B (280-320 nm) radiation or by cis urocanic acid.

Carnosine is a naturally occurring histidine-containing dipeptide in mammalian tissues for which a physiological role has not been defined. It has antioxidant properties, but has also been shown to be related metabolically to histidine and histamine, and to have immunopotentiating properties in vivo. It is shown here that carnosine presented topically or in the diet, potentiated the contact hypersensitivity reaction in hairless mice. Carnosine also prevented the systemic suppression of this reaction following exposure of the dorsal skin to ultraviolet B (UVB) radiation. Furthermore, carnosine prevented the systemic suppression caused by a topically applied lotion containing cis urocanic acid, indicating that it may act in competition with this UVB photoproduct which is believed to initiate many of the suppressive effects of UVB radiation.

Administration, Cutaneous↗

PubMed1991

Ultraviolet radiation-induced murine tumors produced in the absence of ultraviolet radiation-induced systemic tumor immunosuppression.

Using micro-UV-irradiation versus whole-dorsal irradiation for inducing cutaneous carcinomas in Skh:HRI mice and an assay for UV radiation (UVR)-induced systemic tumor immunosuppression, the dependence upon systemic immunosuppression for the growth of UVR-induced carcinomas was examined. Squamous cell carcinomas were produced by repeated microirradiation of 0.8-cm2 middorsal skin with xenon are solar-simulated UVR. These tumors were excised from tumor-bearing animals who 7 days later were inoculated ventrally with a cloned UVR-induced squamous cell carcinoma cell line, the T51/6. This cell line only grows in UVR-induced immunosuppressed Skh:HRI mice. In two separate experiments T51/6 inocula failed to grow significantly in the previously tumor-bearing animals (1 of 13) and in unirradiated mice (0 of 19), whereas it grew in 100% (15 of 15) of animals given a whole-dorsal subcarcinogenic UVR dose from a filtered fluorescent tube solar simulator. No sinecomitant immune response to the T51/6 was found in previously UVR-induced tumor-bearing animals. In contrast to whole-dorsal UVR-induced tumors, microirradiation-induced squamous cell carcinomas, whose original growth environment lacked UVR-induced systemic tumor immunosuppression, did not grow preferentially in mice given an immunosuppressive dose of UVR. However both the whole-dorsal and microirradiation-induced tumors were shown to be poorly antigenic, since they lacked preferential growth in athymic nude mice. These observations provide evidence that UVR-induced systemic tumor immunosuppression is not necessary for the production of UVR-induced tumors. However, it does cause a positive selection pressure during tumor formation, independent of the carcinogenic effect of UVR, which affects the transplantation biology of a tumor.

Animals↗

PubMed1991

Differential protection by two sunscreens from UV radiation-induced immunosuppression.

A controversy has arisen concerning the ability of sunscreens to protect mice from the immunosuppressive effects of UV radiation. We have assessed the photoprotection in hairless mice of two sun protection factor (SPF)15 sunscreens containing different UVB (280-320-nm) absorbers, namely, octyl-N-dimethyl-p-aminobenzoate (o-PABA) or 2-ethylhexyl-p-methoxycinnamate (2-EHMC). Following three minimum erythemal exposures to UV radiation, both systemic suppression of contact hypersensitivity to 2,4-dinitrofluorobenzene and induction of susceptibility to transplanted UV radiation-induced tumor cells was established. Topically applied 2-EHMC sunscreen protected totally from both forms of immunosuppression, but the o-PABA sunscreen failed to protect, although both sunscreens were equally effective in protection from UV radiation-induced erythema and edema.

4-Aminobenzoic Acid↗

PubMed1991

Langerhans cell migration into ultraviolet light-induced squamous skin tumors is unrelated to anti-tumor immunity.

There has been much speculation as to the role of Langerhans cells (LC) in the induction of anti-tumor immunity. Whereas there is considerable circumstantial evidence that disruptions in the density and function of these cells during the early stages of ultraviolet (UV) light- and chemical carcinogen-induced carcinogenesis may be important for enabling developing neoplasms to escape immune destruction, the role of the large number of these cells found infiltrating developed skin tumors is less clear. To investigate this we have compared the LC density infiltrating transplanted non-immunogenic and immunogenic UV-induced murine tumors as well as LC in the epidermis overlying the tumors. Whereas two non-immunogenic tumor lines attracted large numbers of Ia+ dendritic cells, an immunogenic tumor line did not. Similar results were obtained whether the tumors were transplanted into syngeneic immunocompetent or athymic immunodeficient mice. Hence, there was no relationship between tumor immunogenicity or host immunocompetence and Ia+ dendritic cell density. Furthermore, there was no correlation with the pattern of T-cell infiltration of the tumors or CD4/CD8 cell ratio. Our results also indicate that whereas UV light decreased Ia+ cell density, both in the epidermis and the tumors, it did not inhibit the tumors from attracting Ia+ dendritic cells. Thus, the Ia+ dendritic cells infiltrating skin tumors are unlikely to indicate a host immune response to the tumor, but are more likely to be attracted by tumor-derived cytokines.

Animals↗

PubMed1991

The effect of the antihistamine cimetidine on ultraviolet-radiation-induced tumorigenesis in the hairless mouse.

This experiment investigated the effect on ultraviolet (UV) radiation-induced tumorigenesis of feeding the histamine type 2 receptor antagonist, cimetidine, to Skh:HR mice. Cimetidine was fed to one group during a 70 day period of chronic UVR (5 days/week for 10 weeks), to a second group from the end of this period to the end of the experiment at 286 days and a third group was fed a control diet only throughout the experiment. Feeding mice cimetidine during the 70 day period of irradiation protected them against the later development of skin tumours.

Animals↗

PubMed1991

Hazards of urocanic acid as a cosmetic ingredient.

Certain commercially available cosmetic products have been found to contain the ingredient urocanic acid. We have shown that the solar irradiation in vitro of one such lotion resulted in the formation of cis urocanic acid. The irradiated lotion, when applied topically to the skin of hairless mice, systemically suppressed the normal contact hypersensitivity reaction to 2,4-dinitrofluorobenzene by 68%. In addition, mice exposed to a minimally erythemal dose of ultraviolet B (280-320 nm) radiation, normally sub-immunosuppressive, showed a 56% suppression of the contact hypersensitivity reaction if they were irradiated through the topically applied cosmetic lotion.

Animals↗

PubMed1990

Effect on topical 5-methoxypsoralen on tumorigenesis induced in albino and pigmented hairless mouse skin by UV irradiation.

A new line of the Skh:HRII hairless pigmented mouse (black juvenile coat) is described which has been selectively bred for the capacity to respond consistently to simulated solar UV radiation with a continuous and strong tan. This mouse demonstrates a degree of protection from chronic UV-induced tumorigenesis when compared with the Skh:HRI hairless albino mouse, and has been used here to study the effect of induced melanogenesis on phototumorigenesis. Mice were irradiated for 10 weeks with incremental doses of simulated solar UV radiation (UVA + B) from a fluorescent tube source which induced tumours in 100% of albino mice and 93% of black mice by 200 days (minimally oedemal), or with 60% of this dose (sub-oedemal) which induced tumours in 85% of albino mice and 65% of black mice. Mice were also exposed to the UVA component of these radiation sources, obtained by window glass filtration. The effect of topical 5-methoxypsoralen (5-MOP) was examined, at either 0.003% with minimally oedemal UVA + B or its UVA component alone, or at 0.01% with sub-oedemal UVA + B or its UVA component alone, in both albino and black mice. The 5-MOP concentrations were selected as the maximum concentration which did not increase the erythema and oedema responses after a single exposure to minimally oedemal or sub-oedemal UVA + B. At 200 days, the tumorigenic response to sub-oedemal UVA + B was significantly increased by topical 5-MOP, to 100% in albinos and 93% in black mice. In contrast, tumorigenesis in response to minimally oedemal UVA + B was unaffected by topical 5-MOP. The UVA component alone of either irradiation regime was not tumorigenic under these conditions. When combined with topical 5-MOP, the UVA of minimally oedemal UVA + B became moderately tumorigenic, and resulted in a tumour incidence of 23% in albinos and 14.5% in black mice. However, the UVA component of sub-oedemal UVA + B, when combined with topical 5-MOP, was highly tumorigenic specifically in albino mice, inducing tumours in 93% of albino mice but in only 27% of black mice. Tan intensity resulting from minimally oedemal UVA + B was not enhanced by topical 5-MOP, and its UVA component combined with 5-MOP resulted in only a minimal tan. However, the tan intensity resulting from sub-oedemal UVA + B with topical 5-MOP was strongly increased, although its UVA component combined with 5-MOP did not produce a perceptible tan.(ABSTRACT TRUNCATED AT 400 WORDS)

5-Methoxypsoralen↗