Feline vaccine-associated sarcomagenesis: Is there an inflammation-independent role for aluminium?

Vet Comp Oncol. 2018 Mar;16(1):E130-E143. doi: 10.1111/vco.12358. Epub 2017 Sep 28.

Abstract

Aluminium has been found in feline vaccine-associated sarcomas. In this study, we investigated the potential for aluminium to contribute directly to tumourigenesis. Our results indicated that an aluminium hydroxide adjuvant preparation was cytotoxic and mutagenic in human-Chinese hamster ovary (CHO) hybrid cells in vitro. Moreover, CHO cells deficient in DNA double strand break (DSB), but not single-strand break (SSB), repair, were particularly sensitive to aluminium exposure compared with repair proficient cells, suggesting that aluminium is associated with DSBs. In contrast to CHO cells, primary feline skin fibroblasts were resistant to the cytotoxic effects of aluminium compounds and exposure to an aluminium chloride salt promoted cell growth and cell cycle progression at concentrations much less than those measured in particular feline rabies vaccines. These findings suggest that aluminium exposure may contribute, theoretically, to both initiation and promotion of tumours in the absence of an inflammatory response.

Keywords: DNA damage; Mutation; aluminium; cell cycle; double-strand break; feline vaccine-associated sarcoma; fibroblasts.

MeSH terms

  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Immunologic / therapeutic use
  • Aluminum Chloride
  • Aluminum Compounds / adverse effects*
  • Aluminum Compounds / therapeutic use
  • Animals
  • CHO Cells / drug effects
  • Cat Diseases / chemically induced
  • Cat Diseases / etiology*
  • Cats
  • Cell Cycle / drug effects
  • Chlorides / adverse effects*
  • Chlorides / therapeutic use
  • Cricetulus
  • DNA Breaks, Double-Stranded / drug effects
  • Female
  • Fibroblasts / drug effects
  • Inflammation / chemically induced
  • Inflammation / veterinary*
  • Male
  • Sarcoma / chemically induced
  • Sarcoma / etiology
  • Sarcoma / veterinary*
  • Skin / drug effects
  • Soft Tissue Neoplasms / chemically induced
  • Soft Tissue Neoplasms / etiology
  • Soft Tissue Neoplasms / veterinary*
  • Vaccines / adverse effects*

Substances

  • Adjuvants, Immunologic
  • Aluminum Compounds
  • Chlorides
  • Vaccines
  • Aluminum Chloride