Updated soil to fruit concentration ratios for radiocaesium compiled under the IAEA MODARIA II Programme.

Under the International Atomic Energy Agency (IAEA) Modelling and Data for Radiological Impact Assessments (MODARIA II) Programme, Working Group 4 activities included collating radionuclide transfer data from Japan following the Fukushima Daiichi Nuclear Power Plant accident and separately collating concentration ratio (CR) data for root uptake of radionuclides by crops grown in tropical and arid climates. In this paper, the newly compiled radiocaesium CR data for fruit from Japan, tropical and arid climates have been combined with the data originally compiled for the IAEA Technical Reports Series No. 472 (TRS 472) and additional data identified from the literature to produce an enhanced MODARIA II dataset of fruit radiocaesium CR values. Statistical analysis of the MODARIA II dataset by climate class (based on the Köppen-Geiger climate classification) indicated that the CR values for tropical climates were significantly higher (p< 0.05) than those for arid, temperate and cold climates. Statistical analysis of the MODARIA II dataset by soil group (based on soil texture) indicated that the CR values for coral sand soil (tropical climates only) and organic soil (temperate climates only) were significantly higher (p< 0.05) than those for the clay, loam and sand soil groups. Statistical analysis of the MODARIA II dataset by plant group (based on plant morphology) indicated that the CR values for non-woody trees (tropical climate bias) were significantly higher (p< 0.05) than those for herbaceous plants, shrubs and woody trees. Comparison of the MODARIA II dataset with original TRS 472 values showed only small changes in the fruit radiocaesium CR values for herbaceous plants and shrubs in temperate climates. There was a decrease in the CR values for woody trees in temperate climate across all soil groups. There was also a decrease in the CR values for tropical climates for all comparable soil groups.

Mitochondria and cancer: past, present, and future.

The area of mitochondrial genomics has undergone unprecedented growth over the past several years. With the advent of the age of omics, investigations have reached beyond the nucleus to encompass the close biological communication and finely coordinated interactions between mitochondria and their nuclear cell mate. Application of this holistic approach, to all metabolic interactions within the cell, is providing a more complete understanding of the molecular transformation of the cell from normal to malignant behavior, before histopathological indications are evident. In this review the surging momentum in mitochondrial science, as it relates to cancer, is described in three progressive perspectives: (1) Past: the historical contributions to current directions of research; (2) Present: Contemporary findings, results and approaches to mitochondria and cancer, including the role of next generation sequencing and proteomics; (3) FUTURE: Based on the present body of knowledge, the potential assets and benefits of mitochondrial research are projected into the near future.

Tomato paste rich in lycopene protects against cutaneous photodamage in humans in vivo: a randomized controlled trial.

BACKGROUND: Previous epidemiological, animal and human data report that lycopene has a protective effect against ultraviolet radiation (UVR)-induced erythema. OBJECTIVES: We examined whether tomato paste--rich in lycopene, a powerful antioxidant--can protect human skin against UVR-induced effects partially mediated by oxidative stress, i.e. erythema, matrix changes and mitochondrial DNA (mtDNA) damage. METHODS: In a randomized controlled study, 20 healthy women (median age 33 years, range 21-47; phototype I/II) ingested 55 g tomato paste (16 mg lycopene) in olive oil, or olive oil alone, daily for 12 weeks. Pre- and postsupplementation, UVR erythemal sensitivity was assessed visually as the minimal erythema dose (MED) and quantified with a reflectance instrument. Biopsies were taken from unexposed and UVR-exposed (3 × MED 24 h earlier) buttock skin pre- and postsupplementation, and analysed immunohistochemically for procollagen (pC) I, fibrillin-1 and matrix metalloproteinase (MMP)-1, and by quantitative polymerase chain reaction for mtDNA 3895-bp deletion. RESULTS: Mean ± SD erythemal D(30) was significantly higher following tomato paste vs. control (baseline, 26·5 ± 7·5 mJ cm(-2); control, 23 ± 6·6 mJ cm(-2); tomato paste, 36·6 ± 14·7 mJ cm(-2); P = 0·03), while the MED was not significantly different between groups (baseline, 35·1 ± 9·9 mJ cm(-2); control, 32·6 ± 9·6 mJ cm(-2); tomato paste, 42·2 ± 11·3 mJ cm(-2)). Presupplementation, UVR induced an increase in MMP-1 (P = 0·01) and a reduction in fibrillin-1 (P = 0·03). Postsupplementation, UVR-induced MMP-1 was reduced in the tomato paste vs. control group (P = 0·04), while the UVR-induced reduction in fibrillin-1 was similarly abrogated in both groups, and an increase in pCI deposition was seen following tomato paste (P = 0·05). mtDNA 3895-bp deletion following 3 × MED UVR was significantly reduced postsupplementation with tomato paste (P = 0·01). CONCLUSIONS: Tomato paste containing lycopene provides protection against acute and potentially longer-term aspects of photodamage.

Real-time polymerase chain reaction analysis of a 3895-bp mitochondrial DNA deletion in epithelial swabs and its use as a quantitative marker for sunlight exposure in human skin.

BACKGROUND: The use of mitochondrial DNA (mtDNA) damage as a reliable and highly sensitive biomarker of ultraviolet (UV) radiation exposure in both the dermis and epidermis has now been well developed by our group and others. We have previously identified a 3895-bp mtDNA deletion which occurred more frequently and to a higher level in usually sun-exposed skin as opposed to occasionally sun-exposed skin. This work focused on older-aged individuals and, in particular, perilesional, histologically normal skin biopsies taken from patients with skin cancer. OBJECTIVES: To develop novel, less-invasive methods of obtaining skin samples (i.e. epidermis) from volunteers covering a much wider age range and larger number of individuals (n = 239). METHODS: The 3895-bp deletion was quantified by a specific real-time polymerase chain reaction assay in normal human epidermis samples taken from three body sites with differing sun exposure. RESULTS: The results show a statistical increase of the level of the 3895-bp deletion with increasing sun exposure in the epidermal swabs of human skin (P < 0·001) and with increasing age of the donor in the needle biopsy samples. CONCLUSIONS: These data suggest that the upper layers of the epidermis are an accessible and reliable site for assessing mtDNA damage caused by UV exposure.

Real-time PCR analysis of a 3895 bp mitochondrial DNA deletion in nonmelanoma skin cancer and its use as a quantitative marker for sunlight exposure in human skin.

Previous findings from our own laboratory have shown that the frequency of occurrence (i.e. the simple presence or absence) of the 3895 bp mitochondrial DNA deletion is increased with increasing sun exposure. The present study has significantly extended this work by developing, validating and then using a quantitative real-time PCR assay to investigate for the first time the actual level (as opposed to the frequency of occurrence) of the 3895 bp deletion in human skin from different sun-exposed body sites and tumours from nonmelanoma skin cancer patients. We investigated the 3895 bp deletion in 104 age-matched split human skin samples taken from various sun-exposed sites defined as usually exposed (n = 60) and occasionally exposed (n = 44) when outdoors. The results clearly show an increased level of the 3895 bp deletion with increasing sun exposure. Specifically, there was a significantly higher level of the deletion in the usually sun-exposed compared to the occasionally sun-exposed skin (P = 0.0009 for dermis, P = 0.008 for epidermis; two-tailed t-test). Our study has also extended previous findings by showing that the level of the 3895 bp deletion is significantly higher in the dermis compared with the epidermis both in the occasionally sun-exposed samples (P = 0.0143) and in the usually sun-exposed skin. (P = 0.0007).

Role of glutathione S-transferase P1, P-glycoprotein and multidrug resistance-associated protein 1 in acquired doxorubicin resistance.

While P-glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1) are known to be important in acquired doxorubicin resistance, the role of glutathione S-transferases (GST) remains unclear. Our study assessed roles of these 3 factors in a human drug-sensitive carcinoma cell line (HEp2), a subclone made resistant by prolonged incubation in doxorubicin (HEp2A), and HEp2 cells stably transfected with human GSTP1. Drug-resistant HEp2A cells showed greater total GST activity, GSTP class enzyme expression, Pgp expression, MRP1 transcript expression, drug efflux and at least 13-fold greater resistance to doxorubicin than the parent HEp2 cell line. GSTM class enzyme expression was similar in both cell types, while GSTA class enzymes were not detected. In the resistant HEp2A cells, cytotoxicity was markedly enhanced by the Pgp/MRP inhibitor verapamil at low doxorubicin concentrations. The GST inhibitor curcumin also enhanced cytotoxicity in HEp2A cells when the Pgp/MRP efflux barrier had been reversed by verapamil or overcome by high doxorubicin concentrations. In addition, curcumin had a chemosensitising effect at low doxorubicin concentrations in HEp2 cells. Stable transfection of HEp2 cells with human GSTP1 increases doxorubicin resistance 3-fold over control cells. Our study indicates involvement of GSTP enzymes as well as efflux mechanisms in the acquired doxorubicin-resistance phenotype.