Abstract:
:Basophilic hepatic foci, nodules, and trabecular hepatocellular carcinomas, collectively referred to as focal hepatic lesions, were induced by single injections of 5.0 micrograms of diethylnitrosamine (DEN) per gram body weight in 15-day-old C57BL/6J X C3HeB/FeJ F1 (B6C3 F1) mice. Groups of eight experimental and eight control mice were killed at 3 days and at 1, 2, 4, 10, 20, 28, 36 and 41 weeks after injection. The only observable acute hepatic toxic effect of DEN, a mild steatosis, was noted at 3 days, but this had disappeared by 7 days following injection. Basophilic foci, composed entirely of altered hepatocytes, were first noted, when very small, at 10 weeks. At later times, some of the foci also contained small collections of proliferated ductules, apparently a result of secondary ingrowth from nearby interlobular bile ducts. The hepatocytes within basophilic foci were characterized by their abundant cytoplasmic RNA, a high nuclear to cytoplasmic ratio (two times greater than normal), which gave them a "crowded appearance," and decreased glucose-6-phosphatase activity. During the course of the study, basophilic foci appeared to increase in size and number. Cytologic anaplasia also became more evident, ultimately culminating in the development of typical trabecular hepatocellular carcinomas by 44 weeks. Invasion of hepatic veins by basophilic foci, first noted at 10 weeks, was prominent by 20 weeks and indicated that many of the lesions manifested this characteristic of malignancy well in advance of the anaplastic features that are also diagnostic of hepatocellular carcinoma. The high growth rates of basophilic foci were confirmed by their greatly increased 3H-thymidine labeling indices, which were 20 times greater than background hepatocytes at 20 weeks following DEN injection. Tumor progression during the course of the study was also suggested by a doubling of labeling indices of hepatocytes in the basophilic foci between 20 to 28 weeks. (The term tumor progression is used in a broad biological sense to encompass any or all of the qualitative and quantitative changes describing the stepwise development of initiated cells to highly malignant neoplasms. This definition differs from the more clinical usage which restricts the process to qualitative changes during the late stages in the development of fully autonomous neoplasms.) An analysis of the number and size of transections through basophilic foci and in some cases, actual reconstructions of the foci from serial sections, indicated that, in aggregate, they grew exponentially between 10 to 36 weeks, with a volume doubling time of 2.5 weeks. The combined morphologic and kinetic data support the view that trabecular hepatocellular carcinomas develop from basophilic foci. Because of their ease of quantitation on conventional H&E stained sections, their rather uniformly spherical shapes, and the high probability of their clonal origin, the induced focal hepatic lesions should provide a useful model for studying tumor growth kinetics during carcinogenesis.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Goldfarb S,Pugh TD,Koen H,He YZdoi
10.1289/ehp.8350149subject
Has Abstractpub_date
1983-04-01 00:00:00pages
149-61eissn
0091-6765issn
1552-9924journal_volume
50pub_type
杂志文章abstract:BACKGROUND:In the developing brain, serotonin (5HT) systems are among the most sensitive to disruption by organophosphates. OBJECTIVES:We exposed neonatal rats to daily doses of diazinon or parathion on postnatal days (PND)1-4 and evaluated 5HT receptors and the 5HT transporter in brainstem and forebrain on PND5, focu...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9337
更新日期:2006-10-01 00:00:00
abstract:BACKGROUND:Human epidemiological and animal studies suggest that developmental exposure to contaminants that activate the aryl hydrocarbon receptor (AHR) lead to suppression of immune system function throughout life. The persistence of immune deficiency throughout life suggests that the cellular target of AHR activatio...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1509820
更新日期:2016-07-01 00:00:00
abstract::Diffuse pulmonary fibrosis is associated with bleomycin administration to humans. The sequential reactions of lung cells to this drug have now been investigated in mice following injection of 20 mg/kg bleomycin twice per week for 4 to 8 weeks. Cytoplasmic and subendothelial edema was first observed in large vessels an...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7616119
更新日期:1976-08-01 00:00:00
abstract::Building-related illness ranges from mild rhinitis to potentially life-threatening hypersensitivity pneumonitis and legionellosis. Sick-building syndrome, consisting of headache, mucous membrane irritation, and fatigue, may be present in 30% of all office workers. Hypersensitivity pneumonitis, asthma, and legionellosi...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.919567
更新日期:1991-11-01 00:00:00
abstract::This article briefly summarizes the epidemiology of the health effects of fine particulate air pollution, provides an early, somewhat speculative, discussion of the contribution of epidemiology to evaluating biologic mechanisms, and evaluates who's at risk or is susceptible to adverse health effects. Based on prelimin...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.108-1637679
更新日期:2000-08-01 00:00:00
abstract::Polycyclic aromatic hydrocarbons (PAHs) are toxic pollutants released by the World Trade Center (WTC) fires and various urban combustion sources. Benzo[a]pyrene (BaP) is a representative member of the class of PAHs. PAH-DNA adducts, or BaP-DNA adducts as their proxy, provide a measure of chemical-specific genetic dama...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7908
更新日期:2005-08-01 00:00:00
abstract::Studies performed earlier have shown a positive relation between blood lead (a parameter for lead body burden) and blood pressure, whereas such a relation between urine cadmium (a parameter for cadmium body burden) and blood pressure could not be shown. Median (i.e., 50th percentile, P50) blood levels in the general p...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.887867
更新日期:1988-06-01 00:00:00
abstract::A comprehensive effort was undertaken to identify articles demonstrating chemical hormesis. Nearly 4000 potentially relevant articles were retrieved from preliminary computer database searches by using various key word descriptors and extensive cross-referencing. A priori evaluation criteria were established including...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.98106s1357
更新日期:1998-02-01 00:00:00
abstract::Using data from published studies, lung concentrations of nickel were compare for persons with and without occupational exposure to nickel. As expected, the concentrations were much higher for persons with occupational exposure. To estimate the effects of nickel-containing tobacco smoke and nickel in the ambient air o...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8981221
更新日期:1989-05-01 00:00:00
abstract::Health is defined as homeostasis of the cellular ecology, and a state where there has not been an inordinate loss, reversible or irreversible, of the structural and/or functional reserves of the body. An adverse health effect is defined as the causation, promotion, facilitation and/or exacerbation of a structural and/...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8352177
更新日期:1983-10-01 00:00:00
abstract:BACKGROUND:Numerous man-made pollutants activate the aryl hydrocarbon receptor (AhR) and are risk factors for type 2 diabetes. AhR signaling also affects molecular clock genes to influence glucose metabolism. OBJECTIVE:We investigated mechanisms by which AhR activation affects glucose metabolism. METHODS:Glucose tole...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1103593
更新日期:2011-12-01 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::High-performance liquid chromatography (HPLC) methods are described which permit the rapid isolation of multiple target macromolecules from the tissues of animals exposed to chemical mutagens. DNA and selected chromosomal proteins are isolated in a simple two step separation scheme. Isolated nuclei are dissolved in 3 ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.856273
更新日期:1985-10-01 00:00:00
abstract::A major challenge in the emerging field of toxicogenomics is to define the relationships between chemically induced changes in gene expression and alterations in conventional toxicologic parameters such as clinical chemistry and histopathology. We have explored these relationships in detail using the rodent uterotroph...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/txg.7345
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:Rates of preterm birth have been rising over the past several decades. Factors contributing to this trend remain largely unclear, and exposure to environmental contaminants may play a role. OBJECTIVE:We investigated the relationship between phthalate exposure and preterm birth. METHODS:Within a large Mexic...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.0800522
更新日期:2009-10-01 00:00:00
abstract::The central feature of hemopoiesis is life-long, stable cell renewal. This process is supported by hemopoietic stem cells which, in the steady state, appear to be dormant in cell cycling. The entry into cell cycle of the dormant stem cells may be promoted by such factors as interleukin-1, interleukin-6 (IL-6), and gra...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.8980199
更新日期:1989-03-01 00:00:00
abstract::In recent years, exposure of man to increasing amounts of metals has occurred rather generally from industrial contamination and variably from intake of dietary mineral supplements. Adverse effects of individual metals can be markedly altered by dietary levels of other essential and nonessential inorganic elements, es...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7825137
更新日期:1978-08-01 00:00:00
abstract::Previously we have demonstrated that several xenobiotics can induce multidrug (mdr) gene expression in cultures of primary isolated hepatocytes. One of the best of these xenobiotic inducers in rat hepatocytes is 2-acetylaminofluorene (2-AAF), which induces mdr expression by an enhancement of mdr gene transcription. In...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.94102s6209
更新日期:1994-10-01 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::Human exposure to carcinogenic Cr(VI) compounds is found among workers in a large number of professional groups, and it can also occur through environmental pollution. A significant number of toxic waste sites contain Cr as a major contaminant. In this paper we summarize our efforts to apply measurements of DNA-protei...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.98106s4969
更新日期:1998-08-01 00:00:00
abstract::Under a mandate from the U.S. Congress, the National Toxicology Program (NTP) of the U.S. Department of Health and Human Services conducts animal bioassays for carcinogenicity of potentially toxic chemicals to which the U.S. population might be exposed. Methyleugenol, a natural as well as synthesized substance, was no...
journal_title:Environmental health perspectives
pub_type: 临床试验,杂志文章
doi:10.1289/ehp.6766
更新日期:2004-05-01 00:00:00
abstract::Although exposure to many industrially important monomers is controlled by law, few of these reactive chemicals have been determined in human tissues. Analogy with other fat-soluble organic substances strongly implies that these monomers may be retained in tissue, subject to the usual physiological constraints of meta...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.7617183
更新日期:1976-10-01 00:00:00
abstract::The N-oxidation of carcinogenic arylamines to form N-hydroxy arylamines has long been regarded as a necessary metabolic step for conversion to proximate carcinogenic derivatives. In contrast, arylamine ring-oxidation has been generally considered to be an important detoxification mechanism. Both enzymatic reactions ar...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9087233
更新日期:1990-07-01 00:00:00
abstract::Dose influences mechanism; and over a wide range of doses, one can envision that mechanism will change with changing dose. This basic concept in toxicology is juxtaposed with the biologic importance of maintaining normal DNA methylation status to provide the focus of this paper. The idea that altered DNA methylation p...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.98106s1285
更新日期:1998-02-01 00:00:00
abstract::The binary, ternary, quaternary, and quintary interactions of a five-component mixture of carcinogenic environmental polycyclic aromatic hydrocarbons (PAHs) using response surface analyses are described. Initially, lung tumor dose-response curves in strain A/J mice for each of the individual PAHs benzo[a]pyrene (B[a]P...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.98106s61337
更新日期:1998-12-01 00:00:00
abstract::This article reviews the epidemiologic studies of the association of ischemic heart disease risk and environmental tobacco smoke (ETS) exposure from a spouse who smokes. Seventeen studies (nine cohort, eight case-control) comprising more than 485,000 lifelong nonsmokers and 7,345 coronary heart disease (CHD) events we...
journal_title:Environmental health perspectives
pub_type: 杂志文章,meta分析
doi:10.1289/ehp.99107s6841
更新日期:1999-12-01 00:00:00
abstract::The historical exposures to aromatic amines of various occupational groups are briefly reviewed. Modern studies indicate that other occupational groups might have risks worth investigating; these include machinists and workers in the chemical industry. Details of a recent investigation into the exposure of dye workers...
journal_title:Environmental health perspectives
pub_type: 历史文章,杂志文章
doi:10.1289/ehp.834913
更新日期:1983-03-01 00:00:00
abstract::Children are uniquely vulnerable to toxic chemicals in the environment. Among the environmental toxicants to which children are at risk of exposure are endocrine disruptors (EDs)--chemicals that have the capacity to interfere with hormonal signaling systems. EDs may alter feedback loops in the brain, pituitary, gonads...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.5799
更新日期:2003-10-01 00:00:00
abstract:BACKGROUND:Bisphenol A (BPA) is known to be biologically active in experimental models even at low levels of exposure. However, its impact on endometrial cancer remains unclear. OBJECTIVES:This study aimed to investigate whether lifelong exposure to different doses of BPA induced uterine abnormalities and molecular ch...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP6875
更新日期:2020-12-01 00:00:00
abstract::The rapid development of the chemical industry, combustion of fossil fuels, and smoking of tobacco have resulted in contact of the general population with benzo(a)pyrene and other carcinogenic aromatic hydrocarbons. Persons especially at risk occupationally are those engaged in thermal processing of oil shale, coal, a...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7930185
更新日期:1979-06-01 00:00:00