Repair pathways for radiation DNA damage under normoxic and hypoxic conditions: Assessment with a panel of repair-deficient human TK6 cells.

Various types of DNA lesions are produced when cells are exposed to ionizing radiation (IR). The type and yield of IR-induced DNA damage is influenced by the oxygen concentration. Thus, different DNA repair mechanisms may be involved in the response of normoxic and hypoxic cells to irradiation with IR. However, differences between the repair mechanisms of IR-induced DNA damage under normoxic versus hypoxic conditions have not been clarified. Elucidating the relative contribution of individual repair factors to cell survival would give insight into the repair mechanisms operating in irradiated normoxic and hypoxic cells. In the present study, we used a panel of repair-deficient human TK6 cell lines that covered seven repair pathways. Cells were irradiated with X-rays under normoxic and hypoxic conditions, and the sensitivities of each mutant relative to the wild-type (i.e. relative sensitivity) were determined for normoxic and hypoxic conditions. The sensitivity of cells varied depending on the type of repair defects. However, for each repair mutant, the relative sensitivity under normoxic conditions was comparable to that under hypoxic conditions. This result indicates that the relative contribution of individual repair pathways to cell survival is comparable in normoxic and hypoxic cells, although the spectrum of IR-induced DNA damage in hypoxic cells differs from that of normoxic cells.

Establishment of reference costs for occupational health services and implementation of cost management in Japanese manufacturing companies.

OBJECTIVES: We developed a standardized cost estimation method for occupational health (OH) services. The purpose of this study was to set reference OH services costs and to conduct OH services cost management assessments in two workplaces by comparing actual OH services costs with the reference costs. METHODS: Data were obtained from retrospective analyses of OH services costs regarding 15 OH activities over a 1-year period in three manufacturing workplaces. We set the reference OH services costs in one of the three locations and compared OH services costs of each of the two other workplaces with the reference costs. RESULTS: The total reference OH services cost was 176,654 Japanese yen (JPY) per employee. The personnel cost for OH staff to conduct OH services was JPY 47,993, and the personnel cost for non-OH staff was JPY 38,699. The personnel cost for receipt of OH services-opportunity cost-was JPY 19,747, expense was JPY 25,512, depreciation expense was 34,849, and outsourcing cost was JPY 9,854. We compared actual OH services costs from two workplaces (the total OH services costs were JPY 182,151 and JPY 238,023) with the reference costs according to OH activity. The actual costs were different from the reference costs, especially in the case of personnel cost for non-OH staff, expense, and depreciation expense. CONCLUSIONS: Using our cost estimation tool, it is helpful to compare actual OH services cost data with reference cost data. The outcomes help employers make informed decisions regarding investment in OH services.

[Development of a Crisis Management Manual for Occupational Health Experts].

When crises such as natural disasters or industrial accidents occur in workplaces, not only the workers who are injured, but also those who engage in emergency or recovery work may be exposed to various health hazards. We developed a manual to enable occupational health (OH) experts to prevent health hazards. The manual includes detailed explanations of the characteristics and necessary actions for each need in the list of "OH Needs During Crisis Management" developed after an analysis of eight cases in our previous research. We changed the endings of explanatory sentences so that users could learn how often each need occurred in these eight cases. We evaluated the validity of the manual using two processes: 1) Providing the manual to OH physicians during an industrial accident; 2) Asking crisis management experts to review the manual. We made improvements based on their feedback and completed the manual. The manual includes explanations about 99 OH needs, and users can learn how and what to do for each need during various crisis cases. Because additional OH needs may occur in other crises, it is necessary to collect information about new cases and to improve the comprehensiveness of the manual continuously. It is critical that this crisis management manual be available when a crisis occurs. We need to inform potential users of the manual through various media, as well as by posting it on our website.

What Occupational Health Needs Arise in Workplaces Following Disasters? A Joint Analysis of Eight Cases of Disaster in Japan.

OBJECTIVE: To identify occupational health needs arising after disasters. METHODS: Using semistructured interviews with expert informants, we jointly analyzed the needs arising in eight disaster cases that threatened the lives or health of workers in Japan. RESULTS: Various types of health issues occurred in a wide range of employees. In total, we identified 100 needs in six phases after disasters and classified them across nine categories of worker characteristics. The proportion of health needs on the list that were applicable in each case varied from 13% to 49%. More needs arose when the companies were responsible for the disaster and when employee lives were lost. We also assessed the list as fairly comprehensive. CONCLUSIONS: The list developed in this study is expected to be effective for anticipating occupational health needs after disasters.

Development of cost estimation tools for total occupational safety and health activities and occupational health services: cost estimation from a corporate perspective.

OBJECTIVES: The aim of the present study was to develop standardized cost estimation tools that provide information to employers about occupational safety and health (OSH) activities for effective and efficient decision making in Japanese companies. METHODS: We interviewed OSH staff members including full-time professional occupational physicians to list all OSH activities. Using activity-based costing, cost data were obtained from retrospective analyses of occupational safety and health costs over a 1-year period in three manufacturing workplaces and were obtained from retrospective analyses of occupational health services costs in four manufacturing workplaces. We verified the tools additionally in four workplaces including service businesses. RESULTS: We created the OSH and occupational health standardized cost estimation tools. OSH costs consisted of personnel costs, expenses, outsourcing costs and investments for 15 OSH activities. The tools provided accurate, relevant information on OSH activities and occupational health services. CONCLUSIONS: The standardized information obtained from our OSH and occupational health cost estimation tools can be used to manage OSH costs, make comparisons of OSH costs between companies and organizations and help occupational health physicians and employers to determine the best course of action.

Assessment of the genotoxic potential of nitric oxide-induced guanine lesions by in vitro reactions with Escherichia coli DNA polymerase I.

It has been suggested that carcinogenesis associated with chronic inflammation involves DNA damage by nitric oxide (NO) and other reactive species secreted from macrophages and neutrophils. The guanine moiety of DNA reacts with NO, yielding two major deamination products: xanthine (Xan) and oxanine (Oxa). Oxa reacts further with polyamines and DNA binding proteins to form cross-link adducts. In the present study, we characterized the structure of the cross-link adducts of Oxa with spermine (Oxa-Sp). Spectrometric analysis of Oxa-Sp adducts showed that they are ring-opened adducts of Oxa covalently bonded to the terminal amino (major product) and internal imino (minor product) groups of spermine. To assess genotoxic potential, Xan, Oxa, Oxa-Sp and an abasic (AP) site were site specifically incorporated into oligonucleotide templates. These lesions differentially blocked in vitro DNA synthesis catalyzed by DNA polymerase I Klenow fragment (Pol I Kf). The relative efficiency of translesion synthesis was G (1) > Oxa (0.19) > Xan (0.12) > AP (0.088) > Oxa-Sp (0.035). Primer extension assays with a single nucleotide and Pol I Kf revealed that non-mutagenic dCMP was inserted most efficiently opposite Xan and Oxa, with the extent of primer elongation being 65% for Xan and 68% for Oxa. However, mutagenic nucleotides were also inserted. The extent of primer elongation for Xan was 16% with dTMP and 14% with dGMP, whereas that for Oxa was 49% with dTMP. For Oxa-Sp, mutagenic dAMP (13%) was preferentially inserted. Accordingly, when generated in vivo, Xan and Oxa would constitute moderate blocks to DNA synthesis and primarily elicit G:C to A:T transitions when bypassed, whereas Oxa-Sp would strongly block DNA synthesis and elicit G:C to T:A transversions.