Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

Frequent homozygous deletion of <i>Cdkn2a/2b</i> in tremolite‐induced malignant mesothelioma in rats

Yasumasa Okazaki, Nobuaki Misawa, Shinya Akatsuka, Norihiko Kohyama, Yoshitaka Sekido, Takashi Takahashi, Shinya Toyokuni

Cancer Science · 2020

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Summary

This laboratory study compared the carcinogenic potential of tremolite and anthophyllite asbestos fibres using mesothelial and macrophage cell lines and a rat intraperitoneal injection model. Tremolite proved significantly more cytotoxic to cultured cells and induced diffuse peritoneal fibrosis and malignant mesothelioma in rats, with 62.5% of rat tumours displaying homozygous deletion of Cdkn2a/2b, mirroring the genetic profile of human mesothelioma. The findings suggest tremolite's carcinogenicity relates to persistent cellular damage and frustrated phagocytosis, mediated partly by fibre diameter and length characteristics.

UK applicability

This mechanistic study of asbestos-induced mesothelioma has limited direct application to UK farming systems or food production. However, it may inform occupational health and safety policy regarding asbestos exposure in agricultural and industrial settings where tremolite contamination of talc or other mineral products occurs.

Key measures

Fibre morphology (scanning electron microscopy); cell cytotoxicity (time-lapse microscopy); peritoneal pathology; genomic aberrations by array-based comparative genomic hybridisation; Cdkn2a/2b deletion status

Outcomes reported

The study evaluated cytotoxicity of tremolite and anthophyllite asbestos fibres in mesothelial and macrophage cell lines, and characterised tumour development and genomic changes in a rat intraperitoneal injection model. Homozygous deletion of Cdkn2a/2b, a frequently lost locus in human mesothelioma, was observed in 8 of rat mesotheliomas studied.

Theme
Nutrition & health
Subject
Pesticides, contaminants & food safety
Study type
Research
Study design
Laboratory experimental study with in vitro cell culture and in vivo rat model
Source type
Peer-reviewed study
Status
Published
Geography
Japan
System type
Laboratory / in vitro
DOI
10.1111/cas.14358
Catalogue ID
BFmohg5end-klyjep

Topic tags

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