Induction of Stomach Cancer in Rats and Mice by Halogenated Aliphatic Fumigants

Olson, W. A.; Habermann, R. T.; Weisburger, Elizabeth K.; Ward, Jerrold M.; Weisburger, John H.

doi:10.1093/jnci/51.6.1993

Cited by 188 publications

(44 citation statements)

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“…The tumour that was examined by electron microscopy had infiltrated the B6C3Fl mice, inducing squamous-cell carcinomas of the forestomach in animals of both sexes (Olson et al, 1973;Technical Report Series No. 28, 1978).…”

Section: Resultsmentioning

confidence: 99%

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Morphology of nasal-cavity tumours in rats after chronic inhalation of 1,2-dibromo-3-chloropropane

Reznik¹,

Reznik-Schüller²,

Ward³

et al. 1980

Br J Cancer

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Summary.-Groups of 50 F344 rats of each sex were exposed to 0-6 or 3-0 pts/106 of 1,2-dibromo-3-chloropropane (DBCP) by inhalation for 6 h/day, 5 days/week for 103 weeks. Fifty rats of each sex inhaling filtered air were used as unexposed controls. All survivors were killed at 104 weeks. Up to 93 O of the male and female rats developed neoplasms of the nasal cavity. Most of the tumours were adenomas, squamous-cell papillomas, squamous-cell carcinomas, and adenocarcinomas. In the low-dose group 780, of the tumours in males and 66% in females were benign, whereas in the high-dose groups 89% in males and 76% in females were malignant.Invasion through the cribriform plate into the cerebrum or metastasis to the regional lymph nodes was found in 730% of the carcinomas in males and 51% in females.Electron-microscopic examination suggested that the basal cells of the olfactory epithelium were the site of origin of the poorly differentiated adenocarcinomas.

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Section: Resultsmentioning

confidence: 99%

“…DBCP was carcinogenic in rats and mice when the substance was administered by chronic oral intubation (Olson et al, 1973). When applied to mouse skin, DBCP led to a highly significant incidence of tumours of the lung and stomach (Van Duuren et al, 1979).…”

mentioning

confidence: 99%

Morphology of nasal-cavity tumours in rats after chronic inhalation of 1,2-dibromo-3-chloropropane

Reznik¹,

Reznik-Schüller²,

Ward³

et al. 1980

Br J Cancer

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“…8)) is based on animal studies (6). No information is available about ethylene dibromide-generated mutation spectra of p53 or other genes in tumors.…”

Section: Discussionmentioning

confidence: 99%

“…The position of the peaks relative to the markers in these profiles revealed the nucleotide position where each GSCH 2 CH 2 Cl adduct was formed. Furthermore, by calculating the ratio between the heights of a given peak in the GSCH 2 CH 2 Cl-treated sample and its equivalent in the negative control, it was possible to establish the relative adduction level of every nucleotide along both p53 strands (exons [5][6][7][8].…”

Section: Methodsmentioning

confidence: 99%

S-(2-Chloroethyl)glutathione-generated p53 Mutation Spectra Are Influenced by Differential Repair Rates More than Sites of Initial DNA Damage

Valadez

Guengerich

2004

Journal of Biological Chemistry

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Several steps occur between the reaction of a chemical with DNA and a mutation, and each may influence the resulting mutation spectrum, i.e. nucleotides at which the mutations occur. The half-mustard S-(2-bromoethyl)glutathione is the reactive conjugate implicated in ethylene dibromide-induced mutagenesis attributed to the glutathione-dependent pathway. A human p53-driven Ade reporter system in yeast was used to study the factors involved in producing mutations. The synthetic analog S-(2-chloroethyl)glutathione was used to produce DNA damage; the damage to the p53 exons was analyzed using a new fluorescence-based modification of ligation-mediated polymerase chain reaction and an automated sequencer. The mutation spectrum was strongly dominated by the G to A transition mutations seen in other organisms with S-(2-chloroethyl)glutathione or ethylene dibromide. The mutation spectrum clearly differed from the spontaneous spectrum or that derived from N-ethyl,N-nitrosourea. Distinct differences were seen between patterns of modification of p53 DNA exposed to the mutagen in vitro versus in vivo. In the four p53 exons in which mutants were analyzed, the major sites of mutation matched the sites with long half-lives of repair much better than the sites of initial damage. However, not all slowly repaired sites yielded mutations in part because of the lack of effect of mutations on phenotype. We conclude that the rate of DNA repair at individual nucleotides is a major factor in influencing the mutation spectra in this system. The results are consistent with a role of N 7 -guanyl adducts in mutagenesis.The somatic theory of cancer holds that carcinogens are mutagens, at least with regard to what are classically termed tumor initiators (1-3). In a general model, cells are initiated by damage resulting from a DNA-alkylating agent, yielding mutations that are fixed by subsequent rounds of replication. Mutation spectra are generally observed when chemical damage to the DNA occurs; i.e. the sites of the mutation are not random and are often characteristic of the DNA-damaging agent (4, 5). Sometimes mutant spectra can be measured in tumors (in experimental animals or humans), although the existence of any "hotspots" for mutations does not necessarily indicate that the particular mutation is the cause of the tumor. The biochemical basis for where mutations occur (i.e. the mutant spectrum) is generally not well understood. Mutation resulting from chemical damage to DNA is a multistep process, and the observed mutant spectrum may be the result of events occurring during five or possibly more individual processes: (i) reaction of the chemical with DNA, (ii) further non-enzymatic reactions of the DNA adduct (e.g. opening of the imidazole ring in the case of guanyl-N 7 alkyl adducts), (iii) DNA repair (or, more specifically, resistance to repair), (iv) the action of DNA polymerases, and (v) the biological effect of a particular nucleotide/amino acid change in the phenotypic assay used.Ethylene dibromide (1,2-dibromoethane, BrCH 2 CH 2 ...

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“…1.2-Dibromoethane (DBE; ethylene dibromide) is a halogenated aliphatic hydrocarbon that has been used as a pesticide and gasoline additive and is of concern to humans because of potential industrial and environmental exposures (Brown, 1984;Hanson, 1984). In rodents, DBE induces neoplasms mainly at the site of exposure when administered chronically by gavage or inhalation (Weisburger, 1977;Olson et al, 1973; Wong et al, 1982). Although neoplastic lesions of the liver have been induced by DBE exposure (Wong et al, 1982;Moslen, 1984), the liver and other internal organs appear less sensitive than directly exposed tissues.…”

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confidence: 99%

Compendium of the FY1990 and FY1992 Research Reviews for the Research Methods Branch

Gardner¹

1994

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Public reporting burden for this collection of information is estimated to average I hour per response, including the time for reviewing Instructions, searching existing data sources. gathering and maintaining the data needed, and completing and reviewing the collection of information Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate Approved for public release; distribution unlimited ABSTRACT (Maximum 200 words)Since 1983, the U.S. Army Biomedical Research and Development Laboratory (USABRDL) has conducted a research program focused on the development of new methods for assessing the potential hazards resulting from exposure to chemicals in the workplace or the environment. This research has been conducted both in-house and extramurally and has involved scientists from other Federal agencies, academic institutions, and the private sector. The need to enhance the integration of the research became increasingly evident as the program grew in the late 1980's. This growth came principally as a result of the U.S. Army Corps of Engineers sponsorship of research to develop environmental applications of new, in vivo hazard assessment models for use in the burgeoning Department of Defense environmental remediation program. One of the many uses of these models is to answer the question, "How clean is clean?" and to assist in the establishment of more realistic clean-up goals for hazardous waste sites.An annual research review meeting was undertaken to facilitate the integration and technology transfer of this research program. This publication is the second 14. SUBJECT TERMS Fish, Medaka, Irout, #13.(Continuation) compendium of these meetings.The papers contained in this document are meant to provide the program management staff with an additional means of reviewing the status and progress of extramural and selected in-house studies in the area of new toxicity assessment models. The papers are, therefore, the principal investigators' (PIs') best efforts to characterize the research at the time of the meeting.Some papers cover the results of several years of research and others outline only the planned research of a new project. The data presented and conclusions of the authors represent the best professional judgment of the respective PI at the time of the workshop but are not equivalent to a peer-reviewed report of completed research. NOTICE DisclaimersThe views, opinions, and/or findings contained in this report are those of the author(s) and should not be construed as official Department of the Army position, policy, or decision, unless so designated by official documentation.Citations of commercial organizations or trade names in this paper do not constitute an official Department of the Army endorsement or approval of the products or services of these organizations.Research was conducted in compliance with the Animal Welfare Act, and other Federal statutes and regulati...

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Induction of Stomach Cancer in Rats and Mice by Halogenated Aliphatic Fumigants

Cited by 188 publications

References 0 publications

Morphology of nasal-cavity tumours in rats after chronic inhalation of 1,2-dibromo-3-chloropropane

Morphology of nasal-cavity tumours in rats after chronic inhalation of 1,2-dibromo-3-chloropropane

S-(2-Chloroethyl)glutathione-generated p53 Mutation Spectra Are Influenced by Differential Repair Rates More than Sites of Initial DNA Damage

Compendium of the FY1990 and FY1992 Research Reviews for the Research Methods Branch

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