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C A Chadwick

Publications and source records attributed to C A Chadwick.

22 records · Page 2Linked to original sources
PubMed1993

DNA damage in UV-irradiated human skin in vivo: automated direct measurement by image analysis (thymine dimers) compared with indirect measurement (unscheduled DNA synthesis) and protection by 5-methoxypsoralen.

The incidence of the various types of skin cancer in the general population has been increasing at an annual rate of 2-8% over the past 2 decades. In spite of considerable media coverage on the risk of skin cancer the acquisition of a suntan is still very popular. Thus the UV exposures required for tanning pose a serious carcinogenic risk, particularly to individuals who tan poorly. On the other hand, the presence of natural skin pigment, or the ability to tan easily can protect the skin against some of the harmful effects of subsequent UV exposures (Kollias et al. 1991). We have recently shown (Young et al. 1991) in human volunteers, using an indirect measurement of DNA damage (unscheduled DNA synthesis (UDS) detected by autoradiography), that a tan induced by UV in the presence of a UVB sunscreen (Parsol MCX) preparation containing 5-methoxypsoralen (5-MOP) is more effective at protecting the skin against a subsequent DNA-damaging challenge dose of UV than a tan induced by UV alone, particularly in individuals who tan poorly. No such protection was seen with the same sunscreen lacking 5-MOP. 5-MOP is an ingredient in natural citrus oils and in many other plants. Here we show the same pattern of protective action when measuring, for the first time, DNA damage directly using a monoclonal antibody to thymine dimers (a major category of DNA lesion induced by UV radiation) on fixed human skin sections and automated image analysis. There is a good correlation between UV exposure dose and the levels of thymine dimers in epidermal nuclei. The levels of thymine dimers (measured as absorption by the mean integrated optical density (IOD)) also correlated well with the levels of UDS (grains per nucleus). These findings are of importance in the comparative risk-benefit assessment of sunscreens with and without 5-MOP. The techniques described have applications for measuring other DNA lesions following UV and other exposures.

5-Methoxypsoralen↗
PubMed1991

Photoprotection and 5-MOP photochemoprotection from UVR-induced DNA damage in humans: the role of skin type.

Sites on previously unexposed buttock skin in 18 subjects (skin types I-V) were treated daily for 2 weeks with suberythemogenic doses of solar-simulated radiation (SSR) alone, SSR plus a UVB sunscreen, and SSR plus the same sunscreen with 5-methoxypsoralen at 30 ppm. The three sites of treatment (designated SSR, SSR/S, and SSR/S/5-MOP), and a control site that received no SSR or topical treatment, were challenged with 2MED SSR 1 week after the treatment had ceased. Biopsy samples, taken within 15 min after the challenge dose, were assessed for unscheduled DNA synthesis (UDS, interpreted as a measure of DNA damage), melanin deposition, and stratum corneum thickening. Within a given skin type, when compared with controls, the significant increase in either pigmentation or stratum corneum thickening was similar for SSR and SSR/S/5-MOP. SSR/S inhibited these endpoints. Compared with controls, UDS was significantly reduced in skin types III-V by SSR and in all skin types by SSR/S/5-MOP. SSR/S elicited no effect apart from minimal reductions in skin types IV and V. Thus, the increases in pigmentation and stratum corneum thickening seen in all skin types with SSR and SSR/S/5-MOP were accompanied by reduced UDS in all skin types with SSR/S/5-MOP but only in skin types III-V with SSR. These findings suggest that, although induced pigmentation and stratum corneum thickening may account in part for the reduction of UDS, qualitative differences in induced pigmentation may exist in skin types I-II between SSR and SSR/S/5-MOP treatments. The findings can also be interpreted to indicate that SSR/S/5-MOP treatment can afford protection against DNA damage from subsequent exposure to solar ultraviolet radiation. Risk-benefit considerations on the use of sunscreens with and without 5-MOP are discussed and the conclusion is drawn that the judicious use of 5-MOP sunscreens, particularly in skin types I-II, affords an alternative option to those seeking a suntan.

DNA↗
PubMed1988

Inhibition of UV radiation-induced DNA damage by a 5-methoxypsoralen tan in human skin.

Previously untanned buttock skin of 4 volunteers (skin type II; tan with difficulty as they sunburn easily) was treated with various sunscreen preparations and solar--simulated radiation (SSR) or SSR alone for 2 weeks. One week later, the treatment sites were challenged with a DNA-damaging dose of SSR--twice the minimal erythema dose (2 MED). Skin biopsy samples were assayed for the levels of unscheduled DNA synthesis (a measure of DNA damage), melanin distribution, and skin thickening. 5-Methoxypsoralen-containing sunscreen preparations plus SSR or SSR alone induced melanogenesis and increased the stratum corneum thickness, but only the former regimen afforded a high degree of protection against subsequent SSR-induced DNA damage. 5-Methoxypsoralen-free sunscreen preparations plus SSR induced negligible tanning, skin thickening, and photoprotection. These findings are relevant to the risk-benefit analysis of sunscreen preparations, especially in skin type II, as they provide evidence that a 5-methoxypsoralen-induced tan is protective against the DNA-damaging effects of solar UV radiation, and thus has the potential to reduce the carcinogenic risk of exposure to such radiation.

5-Methoxypsoralen↗