Nasopharyngeal carcinoma (NPC) is a malignancy prevailing in Taiwan, Hong Kong, Southern China, Southeast Asia, and North Africa. Although early-stage NPC responds well to the primary treatment of radio-chemotherapy, the mortality rate of advanced NPC remains high. Therefore, developing new therapies for nasopharyngeal carcinoma is an urgent task. Emodin is an anthraquinone derivative mainly found in Rheum palmatum. Emodin has been found to possess many anti-cancer functions against various types of cancers, but they are less discussed in the treatment of NPC. This review organized the different studies about the anti-NPC activity of emodin and discussed the potential and challenges of emodin treatment in NPC therapy.

Nasopharyngeal carcinoma (NPC) is a rare variety of head and neck cancers. The risk factors include three major causes: genetic factors, viral infection, and environmental and dietary factors. The types of NPC show strong ethnic and geographic variations. The keratinizing and non-keratinizing types are prevalent in the lower incidence regions like North America and Europe; whereas the undifferentiated type is mostly found in the regions with higher incidences like China, North Africa, Arctic, and Nagaland of North-East India. These suggest a possible major role of the internal genetic factors for generation and promotion of this disease. Viral infections might accelerate the process of carcinogenesis by helping in cellular proliferation and loss of apoptosis. Diet and other environmental factors promote these neoplastic processes and further progression of the disease occurs.

In the early 1900s, numerous seminal publications reported that high rates of cancer occurred in certain occupations. During this period, work with infectious agents produced only meager results which seemed irrelevant to humans. Then in the 1980s ground breaking evidence began to emerge that a variety of viruses also cause cancer in humans. There is now sufficient evidence of carcinogenicity in humans for human T-cell lymphotrophic virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human papillomavirus, Epstein-Barr virus, and human herpes virus 8 according to the International Agency for Research on Cancer (IARC). Many other causes of cancer have also been identified by the IARC, which include: Sunlight, tobacco, pharmaceuticals, hormones, alcohol, parasites, fungi, bacteria, salted fish, wood dust, and herbs. The World Cancer Research Fund and the American Institute for Cancer Research have determined additional causes of cancer, which include beta carotene, red meat, processed meats, low fibre diets, not breast feeding, obesity, increased adult height and sedentary lifestyles. In brief, a historical review of the discoveries of the causes of human cancer is presented with extended discussions of the difficulties encountered in identifying viral causes of cancer.

Emerging disinfection by-products (DBPs) in drinking water are an important public health concern. Certain DBPs, such as nitrosamines, are probable carcinogens, and exposure to halogenated DBPs may lead to birth defects. It is difficult to obtain complete separation of nitrosamines by chromatographic techniques. Thus we explored high-field asymmetric waveform ion mobility spectrometry (FAIMS) as an alternative separation technique for the characterization of individual DBPs in a complex matrix. We first used ESI-FAIMS-MS to separate four nitrosamines: N-nitrosodi-n-butylamine (NDBA), N-nitrosodi-n-propylamine (NDPA), N-nitrosopiperidine (NPip), and N-nitrosodiethylamine (NDEA) in the compensation voltage (CV) spectra. The optimal CVs with a fixed dispersion voltage of -4000 V were found to be -1.2 V (NDBA), 2.7 V (NDPA), 7.5 V (NPip) and 10.1 V (NDEA). In addition, FAIMS-MS effectively reduced the chemical noise and dramatically improved the LODs by as much as tenfold compared to the conventional ESI-MS technique. To further improve sensitivity, an on-line CE system was used in combination with FAIMS-MS to take advantage of the higher ionization efficiency. The calibration curves for the four nitrosamines were linear over a range of 5 ng/mL to 1000 ng/mL with an r(2 )value of 0.9929 to 0.9992. To increase sample throughput, a multiple-injection strategy was developed, in which the CV values were preprogrammed so that the FAIMS device allowed different nitrosamines to pass through at selected time windows. The potential application of the proposed method was demonstrated for the analysis of drinking water samples spiked with nitrosamines.

An attempt is made in this review to update the reader on recent developments and progress in the study of cholangiocarcinoma: a major primary carcinoma of the liver with a very poor prognosis. Knowledge of the cell biology and physiological functions of the cholangiocyte has recently so progressed that our understanding of cholangiocarcinogenetic mechanism is expected to follow. The first part of the review deals with semantic problems, temporal changes in the incidence of cholangiocarcinoma and geographic differences in epidemiology, etiologic factors (particularly opistorchiasis in Thailand and hepatolithiasis in the Far East), and discusses a recently disclosed role of hepatitis C virus infection (30% of cholangiocarcinoma patients have antibodies against hepatitis C virus in Japan).

Nasopharyngeal carcinoma (NPC), particularly those tumors endemic to the Far East, commonly harbor Epstein-Barr virus (EBV), thought to serve as an important oncogenic promoter. Human papillomavirus (HPV) is associated with a proportion of upper aerodigestive tract carcinomas. We hypothesized that HPV might also contribute to the pathogenesis of NPC, and we queried whether geographic and racial distinctions may be identified between NPC of the Far East versus those diagnosed in Caucasian American patients with regard to the interrelationship of histologic subtype and viral infection.

Formalin-fixed paraffin-embedded tissue (FFPET) from 30 patients (6 Caucasian Americans, 1 Chinese American, 14 and 9 patients from Korea and China, respectively) were studied using the ligation-dependent polymerase chain reaction (LD-PCR). These cases were histologically classified according to the World Health Organization (WHO) schema for NPC. Consensus target probes complementary to the L1 region of over 30 HPV types, as well as target probes complementary to EBER-1 (EBV-related nontranslated latency-associated RNA), were used to amplify target sequences.

Seven of 30 NPC (23%) contained HPV sequences. There were 6 Caucasian American patients with NPC; 3 cases (50%) were HPV positive (HPV+). Two of these Caucasian Americans had WHO type I tumors: one was HPV+ and EBV negative (EBV-) and the other was HPV-/EBV+. The remaining Caucasian American NPCs were WHO-II/III tumors which tested as follows: two were coinfected with HPV and EBV, the other two contained EBER but not HPV sequences. The single Oriental American patient had a WHO-III NPC which was HPV-/EBV+. Of the Eastern NPC patients, 4 (1 WHO-I, 3 WHO-II/III) of 23 (17%) NPCs contained HPV sequences as well as EBV. Conclusion. Human papillomavirus appears to be uncommonly (17%) associated with NPC in patients from the Far East and was detected more often (50%) in NPC from American Caucasian patients. Some of these tumors conformed to our perceptions and expectations of NPC (eg, WHO-I tumors being EBV-/HPV+ and WHO-III tumors being EBV+/HPV-), but other tumors did not conform to these expectations (eg, WHO-III NPC occasionally harboring both HPV and EBV). There appears to be a broad profile in the relationship between HPV, EBV, and NPC histologic subtype. Unfortunately, the number of American Caucasian cases studied are too small to allow for strong conclusions.

Epidemiological studies show that the consumption of Chinese salted fish is a causative factor for nasopharyngeal carcinoma (NPC) in southern China. In the present study, N-nitrosamines and their precursors were analyzed in 145 samples of cooked, salted fish collected from various areas in China. The results show that N-dimethylnitrosamine (NDMA), N-diethylnitrosamine (NDEA), N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP) were present in the salted fish. Total volatile N-nitrosamines (TVN) in the salted fish were 0.028 to 4.54 mg/kg. The samples from areas with higher NPC risk showed a higher average level of TVN than those from areas of lower NPC risk. Positive correlations were found between the levels of NDMA, NDEA and TVN and mortality from NPC. Although neither the nitrates nor the nitrites in the salted fish were present at significantly high levels, in vitro data regarding nitrosation of salted fish showed that the N-nitrosamine content had increased substantially. The results support the conclusion that the high NPC risk in southern Chinese may be attributed to consumption of salted fish containing high levels of N-nitrosamines.

The study was carried out to observe the effects of Clonorchis sinensis infection on induction of cholangiocarcinoma in Syrian golden hamsters to which 15 ppm dimethylnitrosamine (DMN) solution was administered for 8 weeks. The histopathological changes of the bile duct and liver cells were observed at the 11th week. In six of 8 hamsters (75%) which were treated with DMN and then infected with C. sinensis, the livers developed cholangiocarcinoma at 10 weeks after the infestation of C. sinensis. The features of cholangiocarcinoma lesions were adenomatous or papillary hyperplasia of the bile duct epithelia showing distinct anaplastic changes with mucinous cell metaplasia and necrotic area. In the hamsters which received either DMN or C. sinensis alone, the livers showed only hyperplastic changes of the bile duct epithelial cells. It was suggested that C. sinensis infection and DMN administration could be a synergism on the development of cholangiocarcinoma in Syrian golden hamsters.

Traditional Korean soysauce samples were collected from households in Chinju, Gyeongnam, Korea and analysed for volatile N-nitrosamines. Five of 24 samples contained NDMA (range = 1.6-10.4 micrograms/l) which was the only volatile N-nitroso compound found. Soysauce made from well water contained NDMA more often (4 of 6 samples) than soysauce made from tap water (1 of 18). This suggests that the water source is a determinate in the NDMA content of soysauce, probably due to a higher nitrate content of well water. The source of salt used did not clearly influence NDMA content. Soysauce was prepared in the laboratory using traditional methods but with 0 to 400 mg/l nitrate and in some cases made 6.5 to 65 mM in ascorbic acid and fermented for 120 days. The NDMA content of the samples was positively correlated with increasing nitrate concentration. Nitrate at 400 mg/l resulted in an NDMA content of 203 micrograms/l. Ascorbic acid substantially inhibited NDMA formation. All samples contained large numbers of nitrate reductase-containing organisms (greater than 1 x 10(7) CFU/ml).

Data on occurrence of nitrate, nitrite and N-nitrosocompounds in food and drinking water, and on total dietary intakes are reviewed. Metabolic, toxicological and epidemiological studies are surveyed and the implications with respect to safety evaluation are addressed. It is concluded that, on the basis of recent long-term animal studies and of clinical experience in man, the current Acceptable Daily Intake (ADI) allocated to nitrate by the Joint FAO/WHO Expert Committee on Food Additives of 0-5 mg/kg body weight/day (expressed as sodium nitrate) might be increased to 0-25 mg/kg body weight/day. Based on similar criteria, the ADI for nitrite would be 0-0.1 mg/kg body weight/day (expressed as sodium nitrite). In view of the known carcinogenicity of N-nitrosocompounds, exposure to these compounds in food should be minimized by appropriate technological means, such as lowering the nitrite concentration in preserved foods to the minimum required to ensure microbiological safety and use of inhibitors of nitrosation like alpha-tocopherol or ascorbic acid. Further work is needed to define the minimal levels of nitrite in foods needed to inhibit outgrowth of Clostridium botulinum and toxin production.

This paper reviews, with particular reference to Opisthorchis viverrini, the evidence that opisthorchiasis and clonorchiasis are aetiological factors in the causation of human bile-duct cancer, especially cholangiocarcinoma, and considers the other aetiological factors which may be operating. The epidemiology, pathology in man and experimental animals, and histogenesis of cholangiocarcinoma associated wtih liver-fluke infection are also considered.

Six batches of food traditionally and commonly consumed by southern Chinese, including two samples of dried shrimps and four samples of different species of salted fish, were tested for mutagenic properties using Salmonella typhimurium TA98 and TA1000. Mutagenic activities toward both tester strains were found in all preparations. In most cases, these activities were enhanced by liver microsomal activation. Urine collected from experimental rats regularly fed salted fish also showed mutagenic activity. The level of this activity decreased markedly when the experimental rats were transferred from a salted fish diet to Purina rat chow. Our data suggested the presence of mutagenic/carcinogenic substances in some local preserved foods and at least one of them, salted fish, has been suspected on epidemiological and experimental evidence to be a possible co-carcinogenic factor in the development of nasopharyngeal carcinoma in southern Chinese. Our finding is compatible with this hypothesis.

A rapid gas chromatographic technique has been developed for quantitative estimation of cyclic N-nitrosamines. Cumbersome clean-up procedures are unnecessary and quantitative estimation can be done by injecting hexane extract without further pretreatment. The detection limit for the procedures is ca. 0.5 ng.

A major proportion of bacterial types, common in the gastrointestinal tract of many animals and man, were active in degrading diphenylnitrosamine and dimethylnitrosamine, the former being degraded more rapidly than the latter. At low nitrosamine concentrations (is less than 0.05 micronmol/ml), approximately 55% of added diphenylnitrosamine, 30% of N-nitrosopyrrolidine, and 4% of dimethylnitrosamine were degraded. The route of nitrosamine metabolism by bacteria appears to be different from that proposed for breakdown by mammalian enzyme systems in that carbon dioxide and formate were not produced. In bacteria, the nitrosamines were converted to the parent amine and nitrite ion and, in addition, certain unidentified volatile metabolites were produced from dimethylnitrosamine by bacteria. The importance of bacteria in reducing the potential hazard to man of nitrosamines is discussed.