Effect of age at inoculation of asbestos on occurrence of mesotheliomas in rats

Our plain-English summary of Effect of age at inoculation of asbestos on occurrence of mesotheliomas in rats, by G. Berry, J.C. Wagner (International Journal of Cancer, 1976).

The study

• Authors: G. Berry, J.C. Wagner
• Journal: International Journal of Cancer
• Published: 1976;17(4):477-83
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

An experiment in which rats were injected intrapleurally with asbestos, the injection taking place at an age of either 2 or 10 months, is reported. In the former group 19 out of 48 rats developed a mesothelioma compared with 17 out of 90 in the latter group. However, by considering the two groups at equal times after injection, eliminating the effects of natural mortality and also taking into account that not all of the mesotheliomas were the cause of death, it was shown that the incidence rate of mesotheliomas was significantly higher (p less than 0.01) in the rats injected at age 10 months and the relative rate was estimated as about 4, with 95% confidence limits of 1.5 and 12. An alternative explanation that the mesotheliomas occurred in the two groups at similar rates, except that in the group injected at age 10 months they occurred on average 4 months sooner after injection, is discussed. Two other groups were also injected, one at age 17 months and the other at 22 months. In the former group two early mesotheliomas were observed, 10 and 74 days after injection, but the next was not observed until over a year later. No explanation of this finding could be suggested other than the possibility that these two tumours were not associated with the asbestos treatment.

In plain English

In this animal experiment, Wistar rats received 20 mg of UICC standard reference crocidolite asbestos in the right pleural cavity. Rats were randomly assigned to injection at 2 months (48) or 10 months (90 completing). Of rats injected at 2 months, 19 of 48 (40%) died with a mesothelioma, versus 17 of 90 injected at 10 months. Mean survival after injection was 704 days for rats injected at 2 months and 469 days for those injected at 10 months. At equal times after injection, allowing for other causes of death, the mesothelioma rate was significantly higher (p less than 0.01) in rats injected at 10 months. Two methods, one fitted twice, estimated this at 3.78 (95% confidence limits 1.3 to 11.6), 4.17 (1.5 to 12.1) and 6.58 (1.7 to 43.3) times the younger group's rate. The authors said they could not rule out that tumours appeared about 4 months sooner after injection in the older group. Groups injected at 17 and 22 months produced few tumours. The authors concluded overall risk was greater for rats injected young, who had longer remaining lifetimes.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: intrapleural injection of asbestos in rats, with rats randomly allocated to injection at two different ages; two further non-randomized groups were added later
• Who was studied: Barrier-protected, caesarian-derived Wistar rats bred at the Medical Research Council's Pneumoconiosis Unit, Penarth, Wales, with equal numbers of each sex in the main groups. Group 1 was 48 rats injected at 2 months (59 days) in November 1970; all 48 completed the experiment. Group 2 was planned as 96 rats injected at 10 months in July 1971; the table lists 95 injected and 90 completing. Group 3 was 16 females injected at 22 months in July 1971 (15 completing). Group 4 was 29 males and 83 females injected at 17 months in October 1971 (106 completing). Groups 3 and 4 came from the previous generation of the same stock.
• Exposure: UICC standard reference sample of crocidolite asbestos, 20 mg per rat in physiological saline (50 mg/ml), injected into the right pleural cavity; the dust for groups 1 and 2 came from the same batch
• Main results:
  • Among rats injected at age 2 months, 19 of 48 (40%) died with a mesothelioma; among rats injected at age 10 months, 17 of 90 did
  • Mean survival after injection was 704 days in the group injected at 2 months and 469 days in the group injected at 10 months
  • The first mesothelioma appeared 428 days after injection in the 2-month group and 431 days after injection in the 10-month group
  • At a given time after injection, the mesothelioma incidence rate was significantly higher (p less than 0.01) in rats injected at 10 months than in rats injected at 2 months. For this analysis, 12 rats whose mesotheliomas were judged not to have caused death were counted as dying of other causes.
  • Two methods of analysis estimated the relative mesothelioma rate (10-month group compared with 2-month group). Pike's method gave 3.78 (95% confidence limits 1.3 to 11.6). Pike's method with the lapse period fixed at 270 days gave 4.17 (1.5 to 12.1). Cox's method gave 6.58 (1.7 to 43.3).
  • An alternative model, in which tumours occurred at similar rates but sooner after injection in the 10-month group, estimated the shift at 126 days (95% confidence limits 23 and 211). The data favoured the original model, but only by a relative likelihood of 2.3 to 1.
  • In the group injected at 17 months, four mesotheliomas were found: at 10 days, at 74 days, and two more than 500 days after injection. The group injected at 22 months had no mesotheliomas, and its longest survivor died 425 days after injection. The authors suggested the two early tumours may have been unrelated to the asbestos.
• The authors' conclusion: The authors concluded that the risk of a tumour at any given time after injection was greater in rats injected when older. However, the overall risk, regardless of when the tumour occurred, was greater for rats injected when young, because they had a longer remaining lifetime.
• Limitations the authors state:
  • Only two randomized age groups could be included because of limited resources
  • The two groups added later (17 and 22 months) produced too few tumours to show how the relative rate was affected
  • Cause of death in an individual animal usually could not be determined with certainty
  • The experiment could not rule out the alternative explanation that tumours simply appeared earlier after injection in the older group
  • Fewer rats injected at 2 months developed mesothelioma (40%) than expected from the earlier experiment used for planning, in which 61% did

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Incidence.

Related studies

• Mesotheliomas in rats following inoculation with asbestos — J.C. Wagner, G. Berry (1969)
• Mesotheliomata in rats after inoculation with asbestos and other materials — J.C. Wagner, G. Berry, et al. (1973)
• Mesotheliomas in rats following inoculation with acid-leached chrysotile asbestos and other mineral fibres — G. Monchaux, J. Bignon, et al. (1981)
• Failure to demonstrate tumour-associated transplantation antigens on asbestos-induced mesotheliomas in rats — D.G. Brown, J.C. Wagner, et al. (1980)
• Pathogenesis of experimentally induced asbestos mesothelioma in rats — L.A. Vasilieva, L.N. Pylev, et al. (1998)
• The effects of the inhalation of asbestos in rats — J.C. Wagner, G. Berry, et al. (1974)

Browse more research in International Journal of Cancer, or return to medical research.