Skin can control solar UVR-induced mutations through the epidermis-specific response of mutation induction suppression.

Skin exposure to solar ultraviolet radiation (UVR) has been a major public concern because of its genotoxicity. We established recently three action spectra of UVR biological effects using inflammation, mutagenicity, and mutation induction suppression (MIS) as indicators to evaluate UVR risk for mammalian skin. MIS is an antigenotoxic epidermis-specific response by which the increase of the mutant frequency (MF) levels off above a certain UVR dose. Here, based on these spectra, the mutation load of the skin after sunlight exposure was evaluated utilizing the spectral solar-UVR intensity data which had been measured at Tsukuba, Japan by the Japan Meteorological Agency. We estimated the daily variation of the solar-UVR effectiveness (effect per second) for the three indicators, and revealed that the effectiveness efficiency (effect per dose) of midday sunlight is 3-4-fold higher than those in the early morning and late afternoon. Based on the daily variations of mutagenicity and MIS effectiveness, we further estimated MFs induced after every one-hour sunlight exposure and reached a remarkable prediction that MFs should be suppressed to a constant level during 9:00-15:00 by MIS. The estimates agreed well with the equivalent values directly determined at Sendai, a site close to Tsukuba, although a small difference was detected for the epidermis at the dose range where the suppressed MFs were predicted. We propose the use of observed minimum inflammation/erythema doses to improve the difference. Our method could provide reliable estimates of sunlight genotoxicity to evaluate skin cancer probabilities.

Action spectrum analysis of UVR genotoxicity for skin: the border wavelengths between UVA and UVB can bring serious mutation loads to skin.

UVR causes erythema, which has been used as a standardized index to evaluate the risk of UVR for human skin. However, the genotoxic significance of erythema has not been elucidated clearly. Here, we characterized the wavelength dependence of the genotoxic and erythematic effects of UVR for the skin by analyzing the induction kinetics of mutation and inflammation in mouse skin using lacZ-transgenic mice and monochromatic UVR sources. We determined their action spectra and found a close correlation between erythema and an epidermis-specific antigenotoxic response, mutation induction suppression (MIS), which suppressed the mutant frequencies (MFs) to a constant plateau level only 2-3-fold higher than the background MF at the cost of apoptotic cell death, suggesting that erythema may represent the threshold beyond which the antigenotoxic but tissue-destructive MIS response commences. However, we unexpectedly found that MIS attenuates remarkably at the border wavelengths between UVA and UVB around 315 nm, elevating the MF plateaus up to levels ∼40-fold higher than the background level. Thus, these border wavelengths can bring heavier mutation loads to the skin than the otherwise more mutagenic and erythematic shorter wavelengths, suggesting that erythema-based UVR risk evaluation should be reconsidered.

"Autophagy suite": Atg9 cycling in the cytoplasm to vacuole targeting pathway.

Macroautophagy continues to gather increasing attention because it is connected with a wide range of human pathophysiologies, developmental processes and life span extension. It is also an interesting process from a basic cellular biology standpoint, as it involves dynamic membrane rearrangements and multiple protein-protein interactions. Although macroautophagy can be nonspecific, there are many examples of selective sequestration including pexophagy, mitophagy and the cytoplasm to vacuole targeting (Cvt) pathway. At present, the Cvt pathway is unique in that it is the only example of a biosynthetic use of macroautophagy. Most of the autophagy-related (Atg) proteins are involved in the Cvt pathway, and various types of analyses have placed these proteins at particular stages of the process. For example, Atg9 is the only characterized transmembrane protein that is absolutely required for Cvt vesicle formation, and it is proposed to carry membrane from peripheral donor sites to the phagophore assembly site where the vesicle forms. Additional proteins, including Atg11, Atg23 and Atg27 are involved in this anterograde movement, whereas Atg1-Atg13 and Atg2-Atg18 are required for the retrograde return to the peripheral sites. Even when we illustrate our understanding of these events in a schematic model, however, they are by necessity flat two-dimensional representations, lacking movement and sound. Yet the cell is a living entity that is not well served by this sole method of information display. Accordingly, we decided to present the Cvt pathway as a vibrant, dynamic process by combining science, music and illustration.

Variations and trends of biologically effective doses of solar ultraviolet radiation in Asia, Europe and South America from 1999 to 2007.

Biological monitoring of solar UV radiation using spore dosimeters has been undertaken since the year 1999 at more than 20 sites in Asia, Europe and South America. The monthly-cumulative data to the end of the year 2004 have been presented before. In this paper, successive data to the end of the year 2007 are compiled and the trends and correlation analyses with yearly and monthly average amounts of columnar ozone are presented. Mean yearly doses at 10 northern and 6 southern hemisphere sites exhibited exponential latitudinal gradients with similar slopes indicating a doubling of the dose with the decline of about 14 degrees. Among 12 sites where continual data for more than 6 years were available, increasing trends in yearly UV doses were observed at 11 sites. At one European (Brussels), two tropical Asian (Padang and Denpasar), and two South American (São Martinho and Punta Arenas) sites, decreasing trends of ozone amounts were noted, whereas at the remaining 6 sites (five sites in Japan and Thessaloniki), increasing trends of the UV doses were observed without notable changes, or with an increase at one site (Kiyotake), of the average ozone amounts. At one site (Taipei), the UV doses and the ozone amounts stayed constant. In the monsoon areas, climatic variations and changes, particularly in the extent of cloudiness and frequency of rainfall in summer months, might have been largely responsible for the trends of the UV doses. However, even at these sites, the decreases in the ozone amounts in summer months were frequently observed and might have contributed to the increasing trends of the UV doses. Since each region and locality is unique in climatic and atmospheric conditions, it is not easy to generalize the global trends. However, at many sites involved in this monitoring project, the increases in the biological UV doses during this period seemed to be linked to the decreases in the ozone amounts.

Biological monitoring of solar UV radiation at 17 sites in Asia, Europe and South America from 1999 to 2004.

A small and robust dosimeter for determining the biologically effective dose of ambient UV radiation has been developed using UV-sensitive mutant spores of Bacillus subtilis strain TKJ6312. A membrane filter with four spots of the spores was snapped to a slide mount. The slide was wrapped and covered with two or more layers of polyethylene sheet to protect the sample from rain and snow and to reduce monthly-cumulative doses within the measurable range. From 1999, monthly data were collected at 17 sites for more than 1 year, and data for 4 to 6 consecutive years were obtained from 12 sites. Yearly total values of the spore inactivation dose (SID) ranged from 3200 at subarctic Oulu to 96 000 at tropical Denpasar, and the mean yearly values of SID exhibited an exponential dependence on latitude in both hemispheres with a doubling for about every 14 degrees of change. During the observation period, increasing trends of UV doses have been observed at all sites with more than 5 years of data available. Year-to-year variations at high and middle latitude sites are considered due mostly to climatic variation. At three tropical sites, negative correlations between the yearly doses and the column ozone amounts were observed. The results verified the applicability of spore dosimetry for global and long-time monitoring of solar UV radiation, in particular at tropical sites where no monitoring is taking place.

UV exposure of elementary school children in five Japanese cities.

A 1 week UV-exposure measurement and outdoor-activity pattern survey was conducted for elementary school children for four seasons at five sites in Japan, i.e. Sapporo (43 degrees 05' N, altitude 40 m), Tsukuba (36 degrees 05' N, 20 m), Tokyo (35 degrees 40' N, 45 m), Miyazaki (31 degrees 60' N, 40 m) and Naha (26 degrees 10' N, 5 m), and UV exposure was measured directly and estimated using outdoor-activity records. The study site with largest UV exposure was Miyazaki, a southern rural area. Comparing the results for boys and girls, UV exposure was larger in boys. UV exposure was large in spring and summer and small in winter. The total amount of UV exposure in spring and summer contributed 57.7-73.4% of total exposure for the year. As a whole, 8.1% and 1.8% of the schoolchildren were exposed to more than 1 minimum erythemal dose (MED) and 2 MED of solar UV in a day, respectively. The estimated yearly UV exposure ranged from 49 207 J/m2 in Miyazaki to 31 520 J/m2 in Tsukuba. The actual UV exposure correlated to potential UV exposure, estimated using outdoor-activity records and ambient UV irradiance, but the ratio differed by season and site. The yearly average of percent UV exposure to ambient UV on a horizontal plane ranged from 9.9% in Tokyo to 4.0% in Naha. In the questionnaire survey on outdoor-activity pattern, a short question "How long did you spend time outdoors between 0900 and 1500 h?" gives the best estimates of UV exposure.