The Multiple Chemicals and Actions Model of carcinogenesis. A possible new approach to developing prevention strategies for environmental carcinogenesis.


:The number of definite and probable human chemical carcinogens identified by IARC approaches between 1987 and June 2004 is reported to be 50 agents. However, overall, given the rapid expansion in the number of chemicals in use, the throughput of the current approach to identifying potential environmental carcinogens is low. The long-term rodent bioassay, a key part of the current approach, identifies many chemicals which eventually turn out to be irrelevant for human health with regard to cancer. A new approach is suggested which focuses on identifying the potency of environmental mixtures for induction of toxicological changes relevant to carcinogenesis (e.g., cell proliferation, chronic inflammation, inhibition of apoptosis, mutagenicity). Details regarding a suggested strategy for prioritization of mixtures are provided with more detailed information regarding mutagenicity as an end point. The long-term rodent bioassay is not included in the proposal (although it is acknowledged that it will continue to be important in premarketing regulatory schemes) for hazard identification. The Multiple Chemicals and Actions Model (MCAM) is developed. In this model the chemical mixtures in the environment act via a number of mechanisms as 'effectors' or 'inhibitors' of a multistage carcinogenic process. Identifying effectors and inhibitors of the rate-limiting step would be important for preventive strategies. Genetic polymorphisms act as modulators of effector and inhibitor mixtures. It is suggested that the MCAM model could be used in public education programmes to help inform on public health issues regarding cancer and to help avoid future scares which tend to focus on single chemicals. It is acknowledged that there would need to be basic research undertaken to generate appropriate data to support the application of the proposal before it could be used in cancer prevention strategies.


Hum Exp Toxicol


Battershill JM




Has Abstract


2005-11-01 00:00:00












  • The ability of Warburgia salutaris extracts to protect against crystalline silica-induced cell injury.

    abstract::In Southern Africa, the medicinal plant Warburgia salutaris is commonly used for the treatment of inflammatory and other diseases. The methanol extracts of W. salutaris were investigated with regard to a) production of proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma; b) a...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Leshwedi M,Steenkamp V,Dutton M,Gulumian M

    更新日期:2008-11-01 00:00:00

  • 3,4-Methylenedioxymethamphetamine causes retinal damage in C57BL/6J mice.

    abstract::3,4-Methylenedioxymethamphetamine (MDMA) is a powerfully addictive psychostimulant with pronounced effects on the central nervous system, but the precise mechanism of MDMA-induced toxicity remains unclear, specifically on the retina. This study was performed to investigate the effects of MDMA treatment on the retina a...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Ma Y,Bian C,Song D,Yao G,Nie R

    更新日期:2020-11-01 00:00:00

  • In vivo and in vitro effects of pentavalent antimony on mouse liver cytochrome P450s.

    abstract::Pentavalent antimonial (Sb5+) drugs such as meglumine antimoniate (MA) are the mainstay treatment of leishmaniases in developing countries. The effects of these compounds on drug-metabolizing enzymes have not been characterized and their potential pharmacokinetic interactions with other drugs are therefore unknown. Th...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Coelho DR,De-Oliveira A,Parente T,Leal BS,das Chagas LF,Oliveira TN,Saint'Pierre TD,Paumgartten F

    更新日期:2017-01-01 00:00:00

  • Differences in the radiotoxicity of two plutonium isotopes in cells in vitro: can they be ascribed to different handling by the cells?

    abstract::Exposure of Co631 cells to plutonium leads to increasing cell death depending on the dose and incubation time. The effects, however, are more pronounced with 239Pu, than with 238Pu. Uptake and binding of the two radionuclides during a 5-h incubation are about equal, but 238Pu is lost more rapidly from the cell. There ...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Boxler C,Rau W,Planas-Bohne F

    更新日期:1992-05-01 00:00:00

  • Serum ammonia as an early predictor of in-hospital mortality in patients with glufosinate poisoning.

    abstract:BACKGROUND:The mortality rate associated with human glufosinate poisoning is high. We evaluated the usefulness of serum ammonia and sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scores for early prediction of in-hospital mortality in glufosinate ammonium po...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Lee J,Lee Y,Kim YS,Choi JG,Go TH,Kim H,Cha YS

    更新日期:2019-09-01 00:00:00

  • Safety evaluation of Elixir Paregorico in healthy volunteers: a phase I study.

    abstract::A liquid alcoholic extract of Papaver somniferum named Elixir Paregorico is extensively used for diarrheal diseases in Brazil. Its increased popularity has brought concerns and fears over the safety of this herbal product. Given the lack of investigative clinical studies, in this regard, this study investigated whethe...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: de Moraes M,Bezerra M,Bezerra F,de Moraes R,Cavalcanti P,Uchoa C,Lima F,Odorico de Moraes M

    更新日期:2008-10-01 00:00:00

  • Features reported after exposure to automatic dishwashing rinse aids.

    abstract:INTRODUCTION:Automatic dishwashing rinse aids are drying aids which contain non-ionic surfactants, usually ethoxylated alcohols, typically at concentrations of ≤30%. OBJECTIVE:To assess the reported toxicity of rinse aids. METHODS:Telephone enquiries to the UK National Poisons Information Service were analysed from J...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Day R,Bradberry SM,Sandilands EA,Thomas S,Thompson JP,Vale JA

    更新日期:2020-06-01 00:00:00

  • Protective potential of 17β-estradiol against co-exposure of 4-hydroxynonenal and 6-hydroxydopamine in PC12 cells.

    abstract::4-hydroxynonenal (4-HNE) and 6-hydroxydopamine (6-OHDA)-mediated damage in dopaminergic neurons is well documented. Protective potential of steroidal hormone (17β-estradiol) has also been suggested. However, therapeutic potential of such promising hormone is hampered due to complex brain anatomy and physiology. Thus, ...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Siddiqui MA,Kashyap MP,Al-Khedhairy AA,Musarrat J,Khanna VK,Yadav S,Pant AB

    更新日期:2011-08-01 00:00:00

  • Amelioration of Benzo[a]pyrene-induced oxidative stress and pulmonary toxicity by Naringenin in Wistar rats: A plausible role of COX-2 and NF-κB.

    abstract::Naringenin is a naturally occurring flavanones and has been found to exhibit free radical scavenging, enzyme inhibition, antioxidants, anti-inflammatory, and anticancer activities. Present study was designed to evaluate the protective role of naringenin against benzo[a]pyrene (B[a]P)-induced oxidative stress and pulmo...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Ali R,Shahid A,Ali N,Hasan SK,Majed F,Sultana S

    更新日期:2017-04-01 00:00:00

  • Changes of acetylcholinesterase activity after long-term exposure to sarin vapors in rats.

    abstract::In our study, rats were exposed to sarin vapors for 240 min at four different concentrations (0.30, 0.43, 0.58 and 0.82 microg/L) in a whole-body inhalation chamber. The acetylcholinesterase activity (AChE, EC was measured in the whole blood, frontal cortex (FC), pontomedullar area (PM) and basal ganglia (BG)...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Bartosova-Sevelova L,Bajgar J

    更新日期:2005-07-01 00:00:00

  • Effects of prenatal PPAR-γ agonist rosiglitazone exposure on rat hippocampus development in a time-dependent manner: A stereological and histopathological study.

    abstract::Rosiglitazone is in the thiazolidinedione class of drugs used in the treatment of type 2 diabetes mellitus. It works as an insulin sensitizer by binding to the peroxisome proliferator-activated receptor gamma. We investigated the effects of prenatally administered rosiglitazone on pyramidal cell numbers and morphologi...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Sağır D,Eren B,Yılmaz BD,Eren Z,Keleş ON,Gökçe AB

    更新日期:2018-08-01 00:00:00

  • Evaluation of biochemical changes in dental tissues after different office bleaching methods.

    abstract::The color of the teeth is an important topic for many people and can be influenced by intrinsic and extrinsic stains. There is an increasing demand for whitening of the teeth year by year. The most popular way of whitening is "bleaching," which is the result of the breakdown of pigments located in the enamel and/or th...

    journal_title:Human & experimental toxicology

    pub_type: 临床试验,杂志文章


    authors: Karaarslan ES,Özmen ZC,Aytac F,Bicakci AA,Buldur M,Aydogan L,Hologlu F,Özkocak B

    更新日期:2019-04-01 00:00:00

  • Hormesis and industrial hygiene: a new hypothesis for low-dose response in occupational risk assessment.

    abstract::The study of Jayjock and Lewis, 'Implication of Hormesis for Industrial Hygiene', represents a challenge for the scientific community to consider hormesis as a possible working hypothesis for redefining risk assessment strategy for low-dose exposures in the realm of industrial hygiene. This invited commentary aims at ...

    journal_title:Human & experimental toxicology

    pub_type: 评论,杂志文章


    authors: Carelli G,Iavicoli I,Castellino N

    更新日期:2002-07-01 00:00:00

  • Celecoxib-induced increase in cytosolic Ca(2+) levels and apoptosis in HA59T human hepatoma cells.

    abstract::Celecoxib has been shown to have antitumor effect in previous studies but the mechanisms are unclear. The effect of celecoxib on cytosolic Ca(2+) concentrations ([Ca(2+)]i) and viability in HA59T human hepatoma cells was explored. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)]i. Celecoxib ...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Cheng HH,Chou CT,Lu YC,Lu T,Chi CC,Tseng LL,Liu SI,Cheng JS,Kuo CC,Liang WZ,Jan CR

    更新日期:2014-11-01 00:00:00

  • Heat-killed probiotic bacteria induce apoptosis of HT-29 human colon adenocarcinoma cell line via the regulation of Bax/Bcl2 and caspases pathway.

    abstract::Apoptosis induction in cancer cells is one of the most efficient ways to treat cancer and find anticancer compounds. The aim of this study was to evaluate the cytotoxic effects of heat-killed indigenous probiotic bacteria and apoptosis induction in the HT-29 human colon adenocarcinoma cell line. The growth-inhibitory ...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Karimi Ardestani S,Tafvizi F,Tajabadi Ebrahimi M

    更新日期:2019-09-01 00:00:00

  • Silibinin mitigates zidovudine-induced hepatocellular degenerative changes, oxidative stress and hyperlipidaemia in rats.

    abstract::Prolonged zidovudine (AZT) treatment in HIV-infected and AIDS patients is shown to induce liver toxicity leading to complications. Therapeutic regimen that could encounter this adverse effect is unavailable and management of toxicity is often symptomatic or is limited to withdrawal of therapy. In the present investiga...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Raghu R,Jesudas B,Bhavani G,Ezhilarasan D,Karthikeyan S

    更新日期:2015-11-01 00:00:00

  • Evaluation of oxidant and antioxidant status in infants with hyperbilirubinemia and kernicterus.

    abstract:OBJECTIVE:The objective of the present study was to determine oxidant and antioxidant status in infants with hyperbilirubinemia and/or kernicterus and to find whether there is a relationship between bilirubin level and oxidant/antioxidant status. PATIENTS:The study includes 69 full-term newborns (neonates with hyperbi...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Doğan M,Peker E,Kirimi E,Sal E,Akbayram S,Erel O,Ocak AR,Tuncer O

    更新日期:2011-11-01 00:00:00

  • An assessment of the in vitro toxicology of Clostridium perfringens type D epsilon-toxin in human and animal cells.

    abstract::The epithelial Madin Darby canine kidney (MDCK) cell line and 17 human cell lines were examined for sensitivity to Clostridium perfringens type D epsilon-toxin. MDCK cells were confirmed as being sensitive to the toxin. In addition, the Caucasian renal leiomyoblastoma (G-402) human cell line was identified as being ep...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Shortt SJ,Titball RW,Lindsay CD

    更新日期:2000-02-01 00:00:00

  • The influence of pharmacological pretreatment on efficacy of HI-6 oxime in combination with benactyzine in soman poisoning in rats.

    abstract::1. The influence of pharmacological pretreatment (pyridostigmine, benactyzine and trihexyphenidyle), designated PANPAL, on soman-induced cholinergic and stressogenic effects as well as on the efficacy of antidotal treatment (HI-6 plus obidoxime) in rats was studied. 2. PANPAL prophylaxis significantly decreased soman-...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Kassa J,Bajgar J

    更新日期:1996-05-01 00:00:00

  • Apoptotic cell death in rat epididymis following epichlorohydrin treatment.

    abstract::Epichlorohydrin (ECH) is an antifertility agent that acts both as an epididymal toxicant and an agent capable of directly affecting sperm motility. This study identified the time course of apoptotic cell death in rat epididymides after ECH treatment. Rats were administrated with a single oral dose of ECH (50 mg/kg). E...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Lee IC,Kim KH,Kim SH,Baek HS,Moon C,Kim SH,Yun WK,Nam KH,Kim HC,Kim JC

    更新日期:2013-06-01 00:00:00

  • Cardiac biomarkers in a model of acute catecholamine cardiotoxicity.

    abstract::Coronary heart disease and in particular its most serious form - acute myocardial infarction (AMI) - represents the most common cause of mortality in developed countries. Better prognosis may be achieved by understanding the etiopathogenetic mechanisms of AMI. Therefore, a catecholamine model of myocardial injury, whi...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Mladenka P,Hrdina R,Bobrovová Z,Semecky V,Vávrová J,Holecková M,Palicka V,Mazurová Y,Nachtigal P

    更新日期:2009-10-01 00:00:00

  • Toxicokinetics of dimethylacetamide (DMAc) in rat isolated perfused liver.

    abstract::Dimethylacetamide (DMAc) is a skin-penetrating solvent able to induce hepatic damage after chronic exposure. Previous research has indicated that metabolism may be saturated at its present TLV/TWA (10 ppm). Biological monitoring of monomethylacetamide (MMAc), the primary metabolite of DMAc, might therefore underestima...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Palmen NG,Evelo CT,Borm PJ,Henderson PT

    更新日期:1993-03-01 00:00:00

  • Reliability of history of acetaminophen ingestion in intentional drug overdose patients.

    abstract::The objective of this study was to determine the reliability of denial of acetaminophen ingestion in intentional drug overdose patients. All intentional drug overdose patients admitted to an emergency department who were able to provide a history were included. A detailed history was obtained on names, timing and numb...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Bentur Y,Lurie Y,Tamir A,Keyes DC,Basis F

    更新日期:2011-01-01 00:00:00

  • Biomonitoring as a tool in the human health risk characterization of dermal exposure.

    abstract::Dermal exposure is an important factor in risk characterization. In occupational settings it becomes relatively more important because of the continuous reduction in inhalation exposure. In the public health arena, dermal exposure may also form a significant contribution to the total exposure. Dermal exposure, however...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Boogaard PJ

    更新日期:2008-04-01 00:00:00

  • Evaluation and comparison of cytotoxicity, genotoxicity, and apoptotic effects of poly-l-lysine/plasmid DNA micro- and nanoparticles.

    abstract::The principal impediment to gene therapy is the development of efficient, nontoxic gene carriers that can handle and deliver foreign genetic materials into various cell types, including healthy and cancerous cells. Poly-l-lysine (PLL) polymers are one of the most favorable gene carriers among nonviral vectors, and PLL...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Alinejad-Mofrad E,Malaekeh-Nikouei B,Gholami L,Mousavi SH,Sadeghnia HR,Mohajeri M,Darroudi M,Oskuee RK

    更新日期:2019-08-01 00:00:00

  • Fluctuation of trace elements during methylmercury toxication and chelation therapy.

    abstract::The aim of the present investigation was to check the fluctuation in essential elements, such as Na, K, Mg, Mn, Cu, Zn, Cr and Ni in the brain, spinal cord, liver and kidney of mice during methylmercury chloride (MMC) toxication and therapy with monothiols (N-acetyl-DL-homocysteine thiolactone and glutathione) and vit...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Bapu C,Purohit RC,Sood PP

    更新日期:1994-12-01 00:00:00

  • Hydrogen sulfide ameliorates cardiovascular dysfunction induced by cecal ligation and puncture in rats.

    abstract::Hydrogen sulfide (H2S) is an endogenously produced gaseous messenger that participates in regulation of cardiovascular functions. This study evaluates the possible protective effect of H2S in cardiovascular dysfunction induced by cecal ligation and puncture (CLP) in rats. After 24 h of induction of CLP, heart rate (HR...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Abdelrahman RS,El-Awady MS,Nader MA,Ammar EM

    更新日期:2015-10-01 00:00:00

  • Defining a tolerable concentration of methanol in alcoholic drinks.

    abstract::Methanol, a potent toxicant in humans, occurs naturally at a low level in most alcoholic beverages without causing harm. However, illicit drinks made from "industrial methylated spirits" [5% (v/v) methanol:95% (v/v) ethanol] can cause severe and even fatal illness. Since documentation of a no-adverse-effect level for ...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Paine A,Davan AD

    更新日期:2001-11-01 00:00:00

  • Clinical features and treatment of Elapidae bites: report of three cases.

    abstract::This report describes two accidents, involving snakes of the Micrurus corallinus species, where compromising respiratory function was not observed and the specific anti-elapidic serum was the single therapy used, and a third incident, probably involving Micrurus frontalis, where neostigmine was used to remedy respirat...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Coelho LK,Silva E,Espositto C,Zanin M

    更新日期:1992-03-01 00:00:00

  • Comparison of VAERS fetal-loss reports during three consecutive influenza seasons: was there a synergistic fetal toxicity associated with the two-vaccine 2009/2010 season?

    abstract::The aim of this study was to compare the number of inactivated-influenza vaccine-related spontaneous abortion and stillbirth (SB) reports in the Vaccine Adverse Event Reporting System (VAERS) database during three consecutive flu seasons beginning 2008/2009 and assess the relative fetal death reports associated with t...

    journal_title:Human & experimental toxicology

    pub_type: 杂志文章


    authors: Goldman GS

    更新日期:2013-05-01 00:00:00