Differentiation of the mechanisms of oncogenicity of 1,4-dioxane and 1,3-hexachlorobutadiene in the rat
Stott, WT; Quast, JF; Watanabe, PG
HERO ID
1937837
Reference Type
Journal Article
Year
1981
Language
English
PMID
| HERO ID | 1937837 |
|---|---|
| In Press | No |
| Year | 1981 |
| Title | Differentiation of the mechanisms of oncogenicity of 1,4-dioxane and 1,3-hexachlorobutadiene in the rat |
| Authors | Stott, WT; Quast, JF; Watanabe, PG |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 60 |
| Issue | 2 |
| Page Numbers | 287-300 |
| Abstract | HEEP COPYRIGHT: BIOL ABS. 1,4-Dioxane (DX) and 1,3-hexachlorobutadiene (HCBD) have induced liver and kidney neoplasms, respectively, upon chronic ingestion of cytotoxic dosages to rats. DX and HCBD were compared in male Sprague-Dawley rats to the genotoxic carcinogen dimethylnitrosamine (DMN) with regard to cytotoxicity (DNA synthesis, histopathology) and genotoxicity (DNA alkylation, in vivo DNA repair). Treatment of rats with tumorigenic dose levels of DX (1 g/kg per day) in drinking water for 11 wk or HCBD (20 mg/kg per d, po) for 3 wk resulted in a 1.5 increase in hepatic DNA synthesis and a 1.8 increase in renal DNA synthesis, respectively. Treatment-related histopathological changes were also observed in treated animals. Cytotoxicity was not detected in rats dosed orally with nontumorigenic levels of DX (10 mg/kg per day), HCBD (0.2 mg/kg per day) or with a tumorigenic dose level of DMN (3 mg/kg per d) for 3 wk. Alkylation of hepatic DNA and DNA repair were not detected in rats dosed with 1 g (14C)DX/kg (po). Renal DNA alkylation (0.78 alkylation/106 nucleotides) and a 1.40 increase in DNA repair were observed in rats dosed with 20 mg (14C)HCBD/kg (po). Neither compound elicited a positive response in the Ames' bacterial mutagenicity or Williams' hepatocyte DNA repair in vitro assay. Rats dosed with 3 mg (14C)DMN/kg po resulted in alkylation of hepatic and renal DNA at levels of 167 and 28.3 alkylations/106 nucleotides, respectively. Large increases in hepatic (3.72 ) and renal (2.87 ) DNA repair were also noted in DMN-dosed rats (20 mg/kg, po). The lack of genotoxic activity by DX and its cytotoxicity at tumorigenic dose levels suggests a nongenetic mechanism of liver tumor induction in rats. Unlike DX, the data suggested that HCBD has a relatively low degree of generic interaction. While kidney tumors, induced only at toxic HCBD doses, may be caused primarily by a nongenetic mechanism, a minor generic contribution cannot be discounted. |
| Doi | 10.1016/0041-008X(91)90232-4 |
| Pmid | 7281189 |
| Wosid | WOS:A1981MF83800014 |
| Url | https://linkinghub.elsevier.com/retrieve/pii/0041008X91902324 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Journal: TOXICOL APPL PHARMACOL 60 ISSN: |
| Is Public | Yes |
| Language Text | English |
| Keyword | Alkylation; Animals; Body Weight/drug effects; Butadienes/toxicity; Carcinogens; DNA/biosynthesis/metabolism; DNA Repair/drug effects; Dimethylnitrosamine/toxicity; Dioxanes/toxicity; Dioxins/toxicity; Organ Size/drug effects; Rats, Inbred Strains; 9007-49-2; CQ8AAO9MO1; J8A3S10O7S; M43H21IO8R |
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