Cell Proliferation and Experimental Liver Cancer

Craddock, Valda M.

doi:10.1016/b978-0-444-41542-4.50012-2

Cited by 101 publications

(29 citation statements)

References 158 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although not a sufficient condition (8,9), cell division seems to be a prerequisite in a number of stages in the process of carcinogenesis. Firstly, the replication of damaged DNA is a necessary event for a successful initiation (10)(11)(12)(13). Secondly, the mitotic activity plays an important role during the period of tumor promotion and progression (14).…”

Section: Introductionmentioning

confidence: 99%

Stimulation of DNA synthesis in rat and mouse liver by various tumor promoters

Büsser

Lutz

1987

Carcinogenesis

View full text Add to dashboard Cite

'To whom reprint requests should be sentIn order to investigate whether the stimulation of liver DNA synthesis might be used to detect one class of hepatic tumor promoters, the incorporation of orally administered radiolabelled thymidine into liver DNA was determined in rats and mice 24 h after a single oral gavage of test compounds at various dose levels. Three DNA-binding hepatocarcinogens, aflatoxin B,~ benzidine and carbon tetrachloride, did not stimulate but rather inhibited DNA synthesis (not for CC1 4 ). Four hepatic tumor promoters, clofibrate, DDT, phenobarbital and thioacetamide, gave rise to a stimulation in a dosedependent manner. Single oral doses between 0.02 and 0.3 mmol/kg were required to double the level of thymidine incorporation into liver DNA (= doubling dose, DD). Differences between species or sex as observed in long-term carcinogenicity studies were reflected by a different stimulation of liver DNA synthesis. In agreement with the bioassay data, aldrin was positive only in male mice (DD = 0.007 mmol/kg) but not in male rats or female mice. 2,3,7,8-TCDD was positive in male mice (DD = 10 ~6 mmol/kg) and in female rats (DD = 2 x 10~6 mmol/kg) but not in male rats. The assay was also able to distinguish between structural isomers with different carcinogenicities.[alpha] Hexachlorocyclohexane stimulated liver DNA synthesis with a doubling dose of about 0.2 mmol/kg in male rats whereas the [gamma]-isomer was ineffective even at 1 mmol/kg. So far, only one result was inconsistent with carcinogenicity bioassay data. The different carcinogenicity of di(2-ethylhexyl)adipate (negative in rats) and di(2-ethylhexyl)phthalate (positive) was not detectable. Both plasticizers were positive in this short-term system with DD's of 0.7 mmol/kg for DEHA and 0.5 mmol/kg for DEHP. The proposed assay is discussed as an attempt to devise short-term assays for carcinogens not detected by the routine genotoxicity test systems.

show abstract

Section: Introductionmentioning

confidence: 99%

Stimulation of DNA synthesis in rat and mouse liver by various tumor promoters

Büsser

Lutz

1987

Carcinogenesis

View full text Add to dashboard Cite

show abstract

“…Similarly, in animals fed on a diet containing AAF, after which a normally subcarcinogenic dose of DMN will induce liver tumours (Becker, 1975), there was an enhanced removal of 06-methylguan ne produced by the DMN (J. D. Buckley & P. J. O'Connor, personal communication). However, as well as increasing DNA repair, these agents are hepatotoxic, and the situation may therefore be comparable with the effect of partial hepatectomy, which increases the number' of cells in pre-replicative DNA synthesis and sensitizes the liver to tumour production (Craddock, 1976).…”

Section: Resultsmentioning

confidence: 99%

Effect of chronic N,N-diethylnitrosamine on the excision of O6-ethylguanine from rat liver DNA

Margison¹,

Curtin²,

Snell³

et al. 1979

Br J Cancer

View full text Add to dashboard Cite

“…Enhanced proliferation can facilitate initiating events, as single-stranded DNA being transcribed or replicated is especially susceptible to mutational events (9). It has been proposed that regenerative cell replication (i.e., in response to tissue injury) is associated with an increased spontaneous mutation rate (38) and elevated numbers of chemically-initi.ated cells (8).…”

Section: Discussionmentioning

confidence: 99%

Pathology and Cell Proliferation Induced by Intra-nasal Instillation of Aldehydes in the Rat: Comparison of Glutaraldehyde and Formaldehyde

1990

View full text Add to dashboard Cite

ABSTRAC~The relative toxicities of formaldehyde and glutaraldehyde to the rat nasal epithelium were determined following intra-nasal instillation of aqueous solutions of these compounds into one nostril of male Fischer 344 (F-344) rats. Lesions identical in appearance to those resulting from acute inhalation exposure to formaldehyde were induced by both compounds in a concentration-dependent manner. Treatments included. India ink or 1 M methylene blue (for instillation deposition studies); sterile saline (vehicle control); 40, 200, 400, and 800 mM formaldehyde; and 10, 20, and 40 mhi glutaraldehyde. Dye-treated rats were sacrificed immediately, and nasal passages were examined to determine the localization of instilled materials. Three days after treatment, all other animals received a single ip injection of 5-bromo12'-deoxyuridine 2 hr prior to sacrifice, and the nasal passages were prepared for histopathology and cell proliferation studies. While sterile saline and 10 mhf glutaraldehydc induced no significant epithelial changes, 20 and 40 mM glutaraldehyde induced extensive lesions in the treated side of the nose. Aldehyde-induced lesions included inflammation, epithclial degeneration, respiratory epithelial hypertrophy, and squamous metaplasia in association with marked increases (3-8-fold) in labeling index for both compounds. Formaldehyde induced similar lesions but required concentrations of 200 mhi or more to elicit a toxic response. Thus, glutaraldehyde is approximately an order of magnitude more toxic to the nasal epithelium than formaldehyde. These studies also indicate that the nose is very resistant to the aldehydes studied, requiring instillation of millimolar concentrations before toxic responses occurred. have been made to model the uptake process (29,30,37). The highly specific localization of nasal lesions induced by inhaled gases in rodents (3,26,27) indicates that these sites may receive a higher dose of the inhaled material. The induction of lesions at these sites may indicate the saturation of airway defenses by an excessively high local dose. Toxic responses to formaldehyde in rodents have been shown to depend upon the concentration of formaldehyde in the inhaled air, rather than on the cumulative exposure (40), but the actual concentration of formaldehyde achieved at the epithelial surface is unknown. The concentration of gas dissolved in surface secretions at these 'hot spots' of deposition also remains to be determined. This information would be of value when attempting to model regional dosimetry of inhaled compounds at specific nasal target sites for inter-species extrapolation (20, 3 6). This article describes the results of studies using an intra-nasal instillation procedure to determine (1) the relative toxicities of formaldehyde and glutaraldehyde, and (2) the approximate concentrations required to induce epithelial damage in the nose of the rat after administration of a single bolus dose ofaldehyde. These studies revealed the relative toxicity of these 2 compounds and demonstrated...

show abstract

Cell Proliferation and Experimental Liver Cancer

Cited by 101 publications

References 158 publications

Stimulation of DNA synthesis in rat and mouse liver by various tumor promoters

Stimulation of DNA synthesis in rat and mouse liver by various tumor promoters

Effect of chronic N,N-diethylnitrosamine on the excision of O6-ethylguanine from rat liver DNA

Pathology and Cell Proliferation Induced by Intra-nasal Instillation of Aldehydes in the Rat: Comparison of Glutaraldehyde and Formaldehyde

Contact Info

Product

Resources

About