Hideki Mori

Members Ahti Anttila, Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Liisankatu 21 B, 00170 Helsinki, Finland Ramesh V. Bhat, National Institute of Nutrition, Indian Council of Medical Research, Jamai-Osmania PO, Hyderabad-500 007 AP, India James A. Bond, Chemico-Biological Interactions, Toxcon, 5505 Frenchmans Creek, Durham, NC 27713, USA Susan J. Borghoff, CIIT Centers for Health Research, 6 Davis Drive, Box 12137, Research Triangle Park, NC 27709-2127, USA F. Xavier Bosch, Epidemiology Unit and Cancer Registry, Catalan Institute of Oncology, Av. Gran via s/n, Km. 2.7, 08907 L’Hospitalet del Llobregat, Spain Gary P. Carlson, School of Health Sciences, 1338 Civil Engineering Building, Purdue University, West Lafayette, IN 47907-1338, USA Marcel Castegnaro, Les Collanges, 07240 Saint-Jean-Chambre, France George Cruzan, ToxWorks, 1153 Roadstown Road, Bridgeton, NJ 08302-6640, USA Wentzel C.A. Gelderblom, Programme on Mycotoxins and Experimental Carcinogenesis, Medical Research Council (MRC), PO Box 19070, Tygerberg, South Africa 7505 Ulla Hass, Institute of Food Safety and Toxicology, Morkhoj Bygade 19, 2860 Soborg, Denmark Sara H. Henry, 5100 Paint Branch Parkway, College Park, MD 20740-3835, USA Ronald A. Herbert, Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, PO Box 12233, Mail Drop B3-08, Research Triangle Park, NC 27709-2233, USA Marc Jackson, Integrated Laboratory Systems, Inc., PO Box 13501, Research Triangle Park, NC 27709, USA IARC WORKING GROUP ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS: SOME TRADITIONAL HERBAL MEDICINES, SOME MYCOTOXINS, NAPHTHALENE AND STYRENE

OBJECTIVE: The aim was to determine whether left ventricular apical myocardium has mechanisms to compensate for sparse sympathetic innervation. METHODS: Contractile and metabolic responses to various adrenergic stimuli and beta adrenergic receptor density were compared between left ventricular basal and apical regions in 26 anaesthetised mongrel dogs, weight 12-28 kg. RESULTS: Regional contractile changes in response to graded cardiac sympathetic nerve stimulation were compared among three basal (anterior, middle, and posterior) regions, and between basal middle and apical regions. There were significant differences in contractile changes among the three basal regions with distinct regions of innervation from right and/or left sided sympathetic ganglia, but not between apical and basal regions. Constant infusion of noradrenaline (0.2-0.4 microgram.kg-1.min-1) produced a greater response in normalised end systolic length in the apical myocardium than in the basal region, at 9.86(SEM 0.06) mm v 10.14(0.04) mm (n = 5, p < 0.025), and a greater increase in tissue cyclic AMP: 1.04(0.20) v 0.60(0.08) pmol.mg-1 (n = 5, p < 0.05). Giving a forskolin derivative (30 micrograms.kg-1, n = 5) produced a greater increase in cyclic AMP in the apical region than in the basal region: 1.26(0.18) v 0.88(0.19) pmol.mg-1 (p < 0.02). beta Adrenergic receptor density in the apical region was greater than in the basal region: 455(45) v 341(35) fmol.mg-1 protein (n = 5, p < 0.05). CONCLUSIONS: Greater beta adrenergic receptor density and/or increased myocardial responsiveness to adenylate stimulation in apical myocardium compensates, at least in part, for its sparse sympathetic innervation.

The chemopreventive effects of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX), on urinary bladder carcinogenesis induced by N-butyl-N(4-hydroxybutyl)nitrosamine (OH-BBN) was investigated in male ICR mice. Mice were given 250 p.p.m. OH-BBN in drinking water for 20 weeks and after a 1 week interval with tap water, water containing AX or CX at a concentration of 50 p.p.m. was administered during subsequent 20 weeks. Other groups of mice were treated with AX or CX alone or untreated. At the end of the study (week 41), the incidences of preneoplastic lesions and neoplasms in the bladder of mice treated with OH-BBN and AX or CX were smaller than those of mice given OH-BBN. In particular, AX administration after OH-BBN exposure significantly reduced the incidence of bladder cancer (transitional cell carcinoma) (P < 0.003). However, the inhibition of the frequencies of such lesions in mice treated with OH-BBN and CX was not significant. Treatment with AX or CX also decreased the number/nucleus of silver-stained nucleolar organizer region proteins (AgNORs), a new index of cell proliferation, in the transitional epithelium exposed to OH-BBN. Preneoplasms and neoplasms induced by OH-BBN, and the antiproliferative potential, was greater for AX than CX. These results indicate that AX is a possible chemopreventive agent for bladder carcinogenesis and such an effect of AX may be partly due to suppression of cell proliferation.

Taurine (T) was first noted as beneficial for stroke and cardiovascular diseases (CVD) prevention in genetic rat models, stroke-prone spontaneously hypertensive rats (SHRSP). The preventive mechanisms of T were ascribed to sympathetic modulation for reducing blood pressure (BP) and anti-inflammatory action. Recent epidemiological surveys revealed the involvement of inflammatory mediators in the pathogenesis of stroke and also atherosclerosis for which T was proven to be effective experimentally. Arterio-lipidosis prone rats, a substrain of SHRSP selectively bred for higher reactive hypercholesterolemia, quickly develop not only arterial fat deposition but also fatty liver which could be attenuated by dietary T supplementation. CARDIAC (CVD and Alimentary Comparison) Study was a WHO-coordinated multi-center epidemiological survey on diets and CVD risks and mortalities in 61 populations. Twenty-four-hour urinary (24U) T was inversely related significantly with coronary heart disease mortality. Higher 24U-T excreters had significantly lower body mass index, systolic and diastolic BP, total cholesterol (T-Cho), and atherogenic index (AI: T-Cho/high density lipoprotein-cholesterol) than lower T excreters. T effects on CVD risks were intensified in individuals whose 24U-T and -magnesium (M) excretions were higher. Furthermore, higher Na excreters with higher heart rate whose BP were significantly higher than those with lower heart rate were divided into two groups by the mean of 24U-T, high and low T excreters. Since the former showed significantly lower BP than the latter, T may beneficially affect salt-sensitive BP rise. Included among the typical 61 populations, were Guiyang, China or St. John's, Newfoundland, Canada where in which the means of both 24U-T and -M were high or low, respectively. The former and the latter had low and high CVD risks, respectively. Australian Aboriginals living at the coastal area in Victoria were supposed to eat T- and M-rich bush and sea foods and be free from CVD 200 years ago, but they presently have nearly the highest CVD risks indicating that T- and/or M-containing seafood, vegetables, fruits, nuts, milk, etc, similar to prehistoric hunters' and gatherers' food should be good for CVD prevention. The preventive effects of T, good for health and longevity, first noted experimentally, were also proven epidemiologically in humans.

Serous cystadenocarcinoma of the pancreas, a rare disease, developed in a 63-year-old Japanese woman. Pathologic examinations of the pancreatic tumor at the subtotal pancreatectomy showed it to be serous cystadenoma with focal atypical lesions. Three years after the operation, however, metastatic liver nodules were found, and the histologic characteristics of these lesions were quite similar to those of the pancreatic neoplasm. Both primary and metastatic tumors were composed of multiple cysts separated by fibrous septa. The epithelium of cysts was cuboidal and had clear cytoplasm, which had positive results for periodic acid-Schiff (PAS) and negative results for PAS with diastase, Alcian blue, and mucicarmine. To the knowledge of the authors, serous cystic neoplasms of the pancreas have been uniformly benign in biologic behavior. Recently, however, serous cystadenocarcinoma of the pancreas has been reported as a new entity. The current case is the second reported case and might support the existence of serous cystadenocarcinoma of the pancreas.