Abstract：
:Current regulatory practices for chemical carcinogens were established when scientific understanding of the molecular mechanisms of chemical carcinogenesis was in its infancy. Initial discovery that DNA mutation was the root of cancer led quickly to regulatory processes that assumed such a simple relationship could be described with a linear approach. This linear, no threshold approach has since become the default approach to risk assessment of chemicals with carcinogenic potential. Since then, a multitude of intrinsic processes have been identified at the molecular, cellular and organism level that work to prevent transient DNA damage from causing permanent mutations, and mutated cells from becoming cancer. Mounting evidence indicates that these protective mechanisms can prevent carcinogenesis at low doses of genotoxic chemicals, leading to non-linear dose-response. Further, a number of non-genotoxic mechanisms have demonstrated threshold-shaped dose-response for cancer outcomes. The existence of non-linear dose-response curves for both non-genotoxic and genotoxic chemical carcinogens stands in stark contrast to the default risk assessment approach that assumes low dose linearity. In this review, we highlight some of the key discoveries and technological advances that have influenced scientific understanding of chemical carcinogenesis over the last fifty years and provide case studies to demonstrate the utility of these modern technologies in providing a biologically robust evaluation of chemical dose-response for cancer risk assessment.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Clewell RA,Thompson CM,Clewell HJ 3rddoi
10.1016/j.cbi.2019.01.025subject
Has Abstractpub_date
2019-03-01 00:00:00pages
112-127eissn
0009-2797issn
1872-7786pii
S0009-2797(18)31446-7journal_volume
301pub_type
杂志文章,评审abstract：:Examination of the high pressure liquid chromatographic profiles of ethyl acetate extractable benzo [a] pyrene (B(a)P)-metabolites from human lung fibroblast and type II epithelial cells after S phase entry indicated that B(a)P-7,8-diol and 9,10-diol species were produced following the oxygenation of B(a)P. These meta...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(85)90009-2
更新日期：1985-12-31 00:00:00
abstract：:Isolated rat hepatocytes were used to investigate the biochemical mechanisms of toxicity of triethyllead (Et3Pb+), a highly neurotoxic degradation product of the antiknocking petrol additive tetraethyllead. As early as 5 min from the addition of 50 microM Et3Pb+ to hepatocyte suspensions a decrease of mitochondrial me...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(94)90111-2
更新日期：1994-01-01 00:00:00
abstract：:The reactive oxygen species (ROS) induced oxidative stress is an inevitable factor for the pathogenesis of cardiovascular diseases. The edible marine algae-derived sulfated polysaccharides gained special attention as novel bioactive compounds having potential pharmacological activities. The present study evaluated in ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.05.044
更新日期：2019-08-01 00:00:00
abstract：:Tumor cells are able to survive and proliferate in spite of their increased oxidative stress. This was taken as a hint for the implication of oxidants/antioxidants in the proliferation of glial-tumor cells. In the present study, an anti-proliferative effect of Naringenin, an antioxidant against cerebrally implanted C6...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2010.09.028
更新日期：2011-01-15 00:00:00
abstract：:Structure-uncoupling activity relationship of seven anthraquinone derivatives were investigated using rat liver mitochondria. Three compounds bearing the free hydroxyl group at the beta-position of their anthraquinone nucleus (1,3,6,8-tetrahydroxyanthraquinone, 1-acetyl-2,4,5,7-tetrahydroxy-9,10-anthracenedione and sk...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(87)90089-5
更新日期：1987-01-01 00:00:00
abstract：:Benzene (B) is a typical micro-pollutant present in air, especially urban air. In this study a possible correlation between personal benzene exposure and S-phenylmercapturic acid (S-PMA) as a biomarker of internal dose was evaluated in a cohort of traffic policemen. The results confirm that S-PMA is significantly corr...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2005.03.028
更新日期：2005-05-30 00:00:00
abstract：:Chronic pancreatitis is characterized by pancreatic fibrosis, associated with excessive activation of pancreatic stellate cells (PSCs) and increased expression of transforming growth factor-β1 (TGF-β1). Recently, our studies have shown that autophagy inhibitor could inhibit PSCs activation and reduce collagen secretio...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.01.005
更新日期：2019-02-25 00:00:00
abstract：:In the present study, we examined the effects of hemin on the mutagenicity of 6-sulfooxymethylbenzo[a]pyrene (SMBP) in Salmonella typhimurium TA98 and Chinese hamster lung fibroblast (V79) cells. The compound was tested for the possible chemoprotective activity against mutagenesis induced by SMBP and its precursor, 6-...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(97)00137-3
更新日期：1998-02-20 00:00:00
abstract：:The present study was an attempt to investigate the hepatoprotective and antioxidative property of Phyllanthus amarus (P. amarus) extract and phyllanthin. Phyllanthin, one of the active lignin present in this plant species was isolated from the aerial parts, by silica gel column chromatography employing gradient eluti...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2009.06.014
更新日期：2009-10-30 00:00:00
abstract：:Glucocorticoids therapy is strongly limited since extended glucocorticoids can cause serious side effects, including increased susceptibility to develop the bone disease osteoporosis. Despite its side effects recognized importance to clinicians, seldom is known about how glucocorticoids directly impact bone-forming os...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2013.11.004
更新日期：2014-01-25 00:00:00
abstract：:Mode of interaction of mercuric mercury and selenite in rabbit blood was investigated in vitro. After the incubation of rabbit blood with 10(-5) M each of 203HgCl2 and Na2(75)SeO3, the amounts of both 203Hg and 75Se incorporated into erythrocytes were markedly larger than the case where the blood was treated separatel...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(83)90111-4
更新日期：1983-03-01 00:00:00
abstract：:Interest in organoselenide chemistry and biochemistry has increased in the past three decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of the organic selenium compound diphenyl diselenide (PhSe)2 (5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced b...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2013.08.002
更新日期：2013-10-25 00:00:00
abstract：:The enzymatic oxidation of tetrachloro-1,4-hydroquinone (1,4-TCHQ), resulting in covalent binding to protein of tetrachloro-1,4-benzoquinone (1,4-TCBQ), was investigated, with special attention to the involvement of cytochrome P-450 and reactive oxygen species. 1,4-TCBQ itself reacted very rapidly and extensively with...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(88)90110-x
更新日期：1988-01-01 00:00:00
abstract：:In a preliminary study screening anti-proliferative natural alkaloids, a very potent benzophenanthridine, chelidonine showed strong cytotoxicity in cancer cells. While several modes of death have been identified, most of anti-cancer attempts have focused on stimulation of cells to undergo apoptosis. Chelidonine seems ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.09.013
更新日期：2014-11-05 00:00:00
abstract：:Intracellular calcium (Ca(2+)i) overload induced by chronic hypoxia alters Ca(2+)i homeostasis, which plays an important role on mediating myocardial injury. We tested the hypothesis that treatment with trimetazidine (TMZ) would improve Ca(2+)i handling in hypoxic myocardial injury. Cardiomyocytes isolated from neonat...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.04.022
更新日期：2015-07-05 00:00:00
abstract：:Nicorandil ameliorated doxorubicin-induced nephrotoxicity; this study aimed to show and explain the mechanism of this protection. A precise method was elucidated to study the effect of nicorandil on doxorubicin-induced nephrotoxicity in rats depending on the critical inflammation pathway TLR4/MAPK P38/NFκ-B. Adult mal...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.108777
更新日期：2019-09-25 00:00:00
abstract：:Ursodeoxycholic acid (UDCA) is a major effective constituent of bear bile powder, which is widely used as function food in China and is documented in the Chinese pharmacopoeia as a traditional Chinese medicine. UDCA has been developed as the only accepted therapy by the US FDA for primary biliary cholangitis. Recently...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.108745
更新日期：2019-09-01 00:00:00
abstract：:Pyridinium oximes are strong nucleophiles and many are effective reactivators of organophosphate-inhibited cholinesterase (ChE). However, the current oxime reactivators are ineffective at crossing the blood-brain barrier and reactivating brain ChE in the intact organism. Our laboratories have developed a series of sub...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.07.004
更新日期：2016-11-25 00:00:00
abstract：:The effect of repeated parenteral administration of cadmium (0.75, 1.5 and 3.0 mg/kg) on tissue disposition and urinary excretion of cadmium, zinc, copper and iron has been studied in the male rat. Cadmium, zinc and copper accumulated in liver and kidney, but the concentration of iron did not alter significantly. The ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(79)90137-6
更新日期：1979-10-01 00:00:00
abstract：:Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes the oxidative phosphorylation of glyceraldehyde 3-phosphate to 1,3-diphosphoglycerate, one of the precursors for glycolytic ATP biosynthesis. The enzyme contains an active site cysteine thiolate, which is critical for its catalytic function. As part of a conti...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2005.05.002
更新日期：2005-06-30 00:00:00
abstract：:The dietary exposure of rats to cadmium (75 ppm) for periods of up to 48 weeks caused an accumulation of cadmium in the femur, and an inhibition of the accumulation of zinc in the bone. After 48 weeks of cadmium treatment, there was a decreased activity of alkaline phosphatase in the femur. This effect was prevented b...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(80)90155-6
更新日期：1980-03-01 00:00:00
abstract：:The present study investigated the protective efficacy of dl-alpha-lipoic acid (LA) on adriamycin (ADR)-induced oxidative damage in rat testis. Adult male albino rats of Wistar strain were administered ADR (1 mg/kg body weight, i.v.), once a week for 10 weeks. ADR injected rats showed increased oxidative stress with a...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2005.12.007
更新日期：2006-03-25 00:00:00
abstract：:Retinoids bearing azido photoaffinity-labeling groups (azidoretinoids) have potential as probes for investigating the molecular mechanisms of action of all-trans-retinoic acid (RA) as mediated by its cellular retinoic acid-binding protein (CRABP) and nuclear receptor proteins. Two new azidoretinoids, 3-azido-4-[2-(5,6...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(90)90072-u
更新日期：1990-01-01 00:00:00
abstract：:Cloning of the androgen and estrogen sulfotransferases has allowed studies on their spatiotemporal regulation and physiological function. These two enzymes appear to be involved in regulating target cell sensitivity for the androgenic and estrogenic steroids. Recombinant androgen sulfotransferase produced in insect Sf...
journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/0009-2797(94)90069-8
更新日期：1994-06-01 00:00:00
abstract：:Butyrylcholinesterase (BChE) is coded by the BCHE gene that presents four exons. The non-codifying exon 1 presents two variants -116G and -116A, being -116A preferentially in cis conformation with the 539T variant (K) of exon 4 which was associated with lower BChE activity and lower body mass index (BMI) variance. Thi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2008.04.019
更新日期：2008-09-25 00:00:00
abstract：:An important application of primary hepatocyte cultures is for hepatotoxicity research. In this paper, gel entrapment culture of rat hepatocytes in miniaturized BAL system were evaluated as a potential in vitro model for hepatotoxicity studies in comparison to monolayer cultures. After exposure for 24 and 48 h to acet...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2006.05.005
更新日期：2006-07-25 00:00:00
abstract：:The extent of DNA modification in cancerous rat live and lung tissues was investigated and compared to their respective normal tissues. Liver tumors were induced by 2-fluorenylacetamide (2-FAA) or N-nitroso-N-2-fluorenylacetamide (N-NO-2-FAA), and lung tumors were induced by sodium nitrite plus trimethylamine. In the ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(94)03327-5
更新日期：1995-02-01 00:00:00
abstract：:Ferulago macrocarpa (Fenzl) Boiss., is an endemic medicinal herb of Iran. In this study a dihydrofuranocoumarin called grandivittin (GRA) was separate and purified from Ferulago macrocarpa (Fenzl) Boiss, and characterized by (1)H NMR and Mass spectroscopic methods. The electrochemical behavior of GRA was evaluated by ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.08.020
更新日期：2016-10-25 00:00:00
abstract：:Tiaprofenic acid is a widely used anti-inflammatory drug; however, the reductive metabolism of tiaprofenic acid is not yet well understood. Here, we compared the reduction of tiaprofenic acid in microsomes and cytosol from the human liver. The microsomes exhibited lower Km value toward tiaprofenic acid than the cytoso...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.03.006
更新日期：2017-10-01 00:00:00
abstract：:This study investigated the spectral interactions of hepatic microsomal cytochrome p450 (CYP) enzymes with four symmetrical polychlorinated biphenyls (PCBs): 2,2',4,4'-tetrachlorobiphenyl (PCB 47); 2,2',5,5'-tetrachlorobiphenyl (PCB 52); 2,2',6,6'-tetrachlorobiphenyl (PCB 54); and 3,3',4,4'-tetrachlorobiphenyl (PCB 77...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2003.09.003
更新日期：2003-12-15 00:00:00
