Abstract:
:Chronic exposure of rodents to high dose levels of drugs, food additives and environmental chemicals frequently results in liver enlargement. Several of these compounds have been found to enhance the incidence of liver tumors in animals briefly exposed previously to hepatocarcinogens. Accordingly, it has been advanced that these agents act as tumor promoters. This contention has remained subject of controversy following reports that these substances may also cause liver tumors in noncarcinogen-treated rodents, particularly in those characterized by a relatively high incidence of "spontaneous" liver tumors. Since many of these chemicals are in common use, a crucial question would seem to be whether such effects are due to facilitation of the expression of pre-existing oncogenic potential, i.e., to tumor promotion, or to the synergistic action of weakly carcinogenic agents. As a result of mechanistic differences tumor promotion and syn-carcinogenesis must exhibit different dose-time-response characteristics, and, accordingly, it should be possible, in principle, to discriminate between these phenomena. However, since tumor manifestation periods in low-dose groups frequently exceed the animals average lifespan, this approach may not always yield conclusive data, unless a sensitive early marker of carcinogenic activity can be employed. There is evidence that enzyme-deficient preneoplastic areas in liver can be used for this purpose. A strong quantitative correlation between carcinogen dose, the extent of ATPase deficient areas, and the subsequent appearance of tumors has now been established for a number of hepatocarcinogens. Experimental data are consistent with the concept that two critical events (hits) are required for induction of ATPase deficiency in hepatocytes. The first hit is carcinogen-dependent, whereas the second hit would seem to be due to time-dependent event(s). Tumor-promoters, such as phenobarbital, were found to accelerate and increase formation of preneoplastic islets. This evidence, together with data indicating that the compound is devoid of carcinogenic potential, suggests that phenobarbital may be operative at relatively early stages of hepatocarcinogenesis by increasing the probability of the occurrence of the time-dependent second hit. Such effects are dose-dependent and appear to be related to the induction of liver enlargement. The changes in hepatocellular ploidy status and atypical nuclear figures observed during phenobarbital treatment and cessation thereof, suggest that this compound might induce abnormal redistributions of genetic material. It is postulated that these cytological changes may result in phenotypical manifestation of recessive oncogenic information.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Kunz HW,Tennekes HA,Port RE,Schwartz M,Lorke D,Schaude Gdoi
10.1289/ehp.8350113subject
Has Abstractpub_date
1983-04-01 00:00:00pages
113-22eissn
0091-6765issn
1552-9924journal_volume
50pub_type
杂志文章abstract::Concentrations of polychlorinated biphenyls (PCBs), hydroxylated metabolites of PCBs (HO-PCBs) and octachlorostyrene (4-HO-HpCS), and pentachlorophenol (PCP) were determined in umbilical cord plasma samples from three different regions of Québec. The regions studied included two coastal areas where exposure to PCBs is...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.02110411
更新日期:2002-04-01 00:00:00
abstract:BACKGROUND:Methylmercury (MeHg) exposure has been linked to an increased risk of coronary heart disease (CHD). Paraoxonase 1 (PON1), an enzyme located in the high-density-lipoprotein (HDL) fraction of blood lipids, may protect against CHD by metabolizing toxic oxidized lipids associated with low-density liproprotein an...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1003296
更新日期:2011-08-01 00:00:00
abstract::The immune system comprises a highly integrated network of multiple tissues and cell types with complicated interactions and effects. It is modulated by the endocrine and nervous systems and there is growing realization of its multifunctionality. The session focusing on immunologic effects of dioxin and related compou...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.95103s2157
更新日期:1995-03-01 00:00:00
abstract::Methylation is considered the detoxification pathway for inorganic arsenic (InAs), an established human carcinogen. Urinary speciation analysis is used to assess the distribution of metabolites [monomethylarsonate (MMA), dimethylarsinate (DMA), and unmethylated arsenic (InAs)], as indicators of methylation capacity. W...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.96104620
更新日期:1996-06-01 00:00:00
abstract::This working paper summarizes the known ultrastructural and biochemical effects of lead, mercury, cadmium, and arsenic on subcellular organelle systems following in vivo administration. Documented metal-induced alterations in nuclear, mitochondrial, microsomal, and lysosomal functions are discussed in relation to thei...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.782237
更新日期:1978-02-01 00:00:00
abstract::Biological monitoring of genotoxic hazard in the rubber industry was performed in 19 male workers and 20 age-matched controls in a local health unit in northern Italy. Peripheral blood lymphocytes were analyzed for the presence of DNA damage (single-cell microgel-electrophoresis, or comet assay) and for cytogenetic pa...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.96104s3543
更新日期:1996-05-01 00:00:00
abstract::In this article we summarize the results of a series of studies that measured the relative bioavailability (RBA) of lead in a variety of soil and soil-like test materials. Reference material (Pb acetate) or Pb-contaminated soils were administered orally to juvenile swine twice a day for 15 days. Blood samples were col...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8852
更新日期:2006-08-01 00:00:00
abstract::The National Cancer Institute (NCI) and the National Toxicology Program (NTP) have carried out a number of laboratory animal carcinogenicity studies and presented the results of these experiments in a series of Technical Reports. This paper tabulates the results of the 327 NCI/NTP studies carried out to date on 308 di...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8774229
更新日期:1987-10-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.02110s61057
更新日期:2002-12-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8669275
更新日期:1986-11-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.02110s2211
更新日期:2002-04-01 00:00:00
abstract:BACKGROUND:Studies on the health effects of polychlorinated biphenyls (PCBs) call for an understanding of past and present human exposure. Time-resolved mechanistic models may supplement information on concentrations in individuals obtained from measurements and/or statistical approaches if they can be shown to reprodu...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1409191
更新日期:2016-03-01 00:00:00
abstract::Bisphenol A (BPA) is the monomer used to manufacture polycarbonate plastic, the resin lining of cans, and other products, with global capacity in excess of 6.4 billion lb/year. Because the ester bonds in these BPA-based polymers are subject to hydrolysis, leaching of BPA has led to widespread human exposure. A recent ...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.7713
更新日期:2005-08-01 00:00:00
abstract::The fundamental problems in population monitoring for genetic effects are twofold: the binomialized nature of the data and the lower power due to small risk of finding positive results. The binomial character is artificial, even forced, and can with advantage be replaced by more refined analysis, and by a focus on all...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8142127
更新日期:1981-12-01 00:00:00
abstract::The Florence Statement on Triclosan and Triclocarban documents a consensus of more than 200 scientists and medical professionals on the hazards of and lack of demonstrated benefit from common uses of triclosan and triclocarban. These chemicals may be used in thousands of personal care and consumer products as well as ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP1788
更新日期:2017-06-20 00:00:00
abstract:BACKGROUND:Although numerous epidemiologic studies now use models of intraurban exposure, there has been little systematic evaluation of the performance of different models. OBJECTIVES:In this present article we proposed a modeling framework for assessing exposure model performance and the role of spatial autocorrelat...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9849
更新日期:2007-08-01 00:00:00
abstract::In the National Toxicology Program 2-year inhalation study of dichloromethane (DCM), there was a significant increase in pulmonary neoplasms in female B6C3F1 mice exposed to 2000 ppm (overall rates of 30/48 versus 5/50 in control). Replicative DNA synthesis was examined to evaluate the potential role of treatment-indu...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.93101s5271
更新日期:1993-12-01 00:00:00
abstract::Mortality curves for groups of fasted male rats treated with single, oral doses of 1,1-dichloroethylene (1,1-DCE, vinylidene chloride) were not monotonically increasing sigmoids, but were complex with maxima or extended plateaus in the region of dose between 100 and 700 mg of 1,1-DCE/kg. The exact shape was a function...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7721157
更新日期:1977-12-01 00:00:00
abstract::Mineral fibers and particulates represent one of the best documented, economically important, and ubiquitously occurring categories of human carcinogens. Yet, while a wealth of information exists concerning the mechanism of action of physical, chemical, and viral carcinogens, virtually nothing is known relative to the...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.803459
更新日期:1980-02-01 00:00:00
abstract:BACKGROUND:Phthalates are metabolized and eliminated in urine within hours after exposure. Several reports suggest that concentrations of phthalate metabolites in a spot urine sample can provide a reliable estimation of exposure to phthalates for up to several months. OBJECTIVES:We examined inter- and intraperson and ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1002231
更新日期:2010-12-01 00:00:00
abstract::A review and summary is given of analytical, biochemical, and immunological studies made following an immunodiagnostic investigation which revealed significant decreases in the numbers, and changes in the functional integrity, of both T-and B-lymphocytes in a group of Michigan dairy farmers exposed to polybrominated b...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8560107
更新日期:1985-05-01 00:00:00
abstract:BACKGROUND:Exposure to arsenic via drinking water is a global environmental health problem. In utero exposure to arsenic via drinking water increases the risk of lower respiratory tract infections during infancy and mortality from bronchiectasis in early adulthood. OBJECTIVES:We aimed to investigate how arsenic exposu...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1205590
更新日期:2013-02-01 00:00:00
abstract:OBJECTIVE:Daily adult human exposure to bisphenol A (BPA) has been estimated at <1 µg/kg, with virtually complete first-pass conjugation in the liver in primates but not in mice. We measured unconjugated and conjugated BPA levels in serum from adult female rhesus monkeys and adult female mice after oral administration ...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.1002514
更新日期:2011-04-01 00:00:00
abstract:BACKGROUND:After Hurricane Katrina, many New Orleans homes remained flooded for weeks, promoting heavy microbial growth. OBJECTIVES:A small demonstration project was conducted November 2005-January 2006 aiming to recommend safe remediation techniques and safe levels of worker protection, and to characterize airborne m...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9258
更新日期:2006-12-01 00:00:00
abstract::Epidemiological studies report a small but positive association between short-term increases in airborne particulate matter and small increases in morbidity and mortality from respiratory and cardiovascular disease in urban areas. However, the lack of a mechanistic explanation to link particle exposure and human healt...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.98106127
更新日期:1998-03-01 00:00:00
abstract::Perinatal exposure to carcinogens may contribute to the determination of susceptibility to cancer in two situations: a) exposure in utero of embryonal or fetal somatic cells to carcinogens, and b) prezygotic exposure of the germ cells of one or both parents to carcinogens. Epidemiological as well as experimental studi...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.929839
更新日期:1992-11-01 00:00:00
abstract:BACKGROUND:The World Health Organization (WHO) released the fourth edition of Guidelines for Drinking-Water Quality in July 2011. In this edition, the 400-µg/L drinking-water guideline for manganese (Mn) was discontinued with the assertion that because "this health-based value is well above concentrations of manganese ...
journal_title:Environmental health perspectives
pub_type: 历史文章,杂志文章
doi:10.1289/ehp.1104693
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by beneficial nutrients in fish containing MeHg...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.1104494
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Fine particulate matter (FPM) in ambient air causes premature mortality due to cardiac disease in susceptible populations. OBJECTIVE:Our objective in this study was to determine the most influential FPM components. METHODS:A mouse model of atherosclerosis (ApoE-/-) was exposed to either filtered air or con...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9150
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND:Drinking water in multiple water districts in the Mid-Ohio Valley has been contaminated with perfluorooctanoic acid (PFOA), which was released by a nearby DuPont chemical plant. Two highly contaminated water districts began granular activated carbon filtration in 2007. OBJECTIVES:To determine the rate of de...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.0901252
更新日期:2010-02-01 00:00:00