Correlations between chemically related site-specific carcinogenic effects in long-term studies in rats and mice

Our plain-English summary of Correlations between chemically related site-specific carcinogenic effects in long-term studies in rats and mice, by J.K. Haseman, A.M. Lockhart (Environmental Health Perspectives, 1993).

The study

• Authors: J.K. Haseman, A.M. Lockhart
• Journal: Environmental Health Perspectives
• Published: 1993;101(1):50-4
• Cited by: 46 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

We examined a database of 379 long-term carcinogenicity studies in rats and mice to evaluate sex and species correlations in site-specific carcinogenic responses. Within a species, most target sites showed a strong correlation between males and females. For example, chemicals producing forestomach or liver tumors in males were likely to produce these same types of tumors in females. There was also a significant correlation between species for certain site-specific carcinogenic effects, most notably tumors of the forestomach, liver, and thyroid gland. In contrast, adrenal pheochromocytoma, preputial/clitoral gland neoplasms, and lung tumors showed no significant interspecies correlation. Many chemicals produced a syndrome of carcinogenic effects involving tumors of the skin, Zymbal gland, preputial/clitoral gland, mammary gland, and/or oral cavity. Regarding different target sites, there appeared to be a correlation between thyroid and liver tumors both within and between species. Further, all chemicals producing mesotheliomas in male rats also produced mammary gland neoplasms in female rats. In contrast, kidney and urinary bladder tumors showed no significant association with any other tumor type in rats or mice. If a chemical produced a site-specific carcinogenic effect in female rats or mice, there was approximately a 65% probability that the chemical would also be carcinogenic at that same site in males. The interspecies correlation was somewhat lower: approximately 36% of the site-specific carcinogenic effects observed in one species (rats or mice) were also observed in the other species.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This study analysed results already collected from 379 long-term cancer studies of chemicals in rats and mice run by the US National Cancer Institute and National Toxicology Program. The authors asked whether a chemical that caused tumors at one body site in one sex or species also caused them in the other sex, in the other species, or at other sites. The article does not discuss asbestos. Agreement between the sexes was high: 66% (97/146) of site-specific effects seen in female rats were also seen in male rats, and 65% (103/159) in mice. Agreement between species was lower: 35% (61/173) of site-specific effects in rats also appeared at the same site in mice. Lung tumors showed no significant link between species. Mesotheliomas were left out of the main analysis because they were rare. Even so, all six chemicals that produced mesothelioma in male rats also produced mammary gland tumors in female rats (p less than 0.0001). The authors concluded that in many cases testing one sex of each species may be enough to detect chemicals that cause cancer in rodents.

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: Statistical analysis of an existing database of long-term rodent carcinogenicity studies, looking at correlations in site-specific tumor responses using Fisher's exact test
• Who was studied: 379 NCI/NTP long-term carcinogenicity studies in rats and/or mice (349 rat studies and 339 mouse studies with adequate experiments in both sexes; 313 studies adequate in all four sex-species groups)
• Exposure: Chemicals tested in NCI/NTP long-term studies, including both carcinogens and noncarcinogens; the analysis covered the 13 most frequent tumor sites. Asbestos is not among the chemicals named.
• Main results:
  • Forestomach showed the greatest male-female consistency: in rats, all 11 studies with forestomach carcinogenicity in females also showed it in males; in mice, 14 of 15 studies showing the effect in one sex showed it in the other
  • A chemical that caused liver tumors in rats was more likely to be a mouse liver carcinogen than one that did not (76% = 25/33 versus 19% = 53/280)
  • Lung tumors showed no significant interspecies correlation: only 2 of 23 chemicals producing lung tumors did so in both rats and mice
  • All six chemicals producing mesothelioma in male rats also produced mammary gland tumors in female rats (p<0.0001)
  • Across the 13 major sites, 35% (61/173) of site-specific effects in rats were also produced in mice at the same site, and 37% (61/167) of effects in mice were also produced in rats
  • Within species, 66% (97/146) of site-specific effects in female rats were also seen in male rats, and 65% (103/159) of effects in female mice were also seen in male mice
  • Kidney and urinary bladder tumors in rats showed no significant association with any other tumor type
  • Of 162 chemicals carcinogenic in at least one of the four sex-species groups, 15 (9%) would not have been detected by testing only male rats and female mice
• The authors' conclusion: The authors concluded that, because males and females respond so similarly, testing one sex of each species may in many cases be sufficient to detect rodent carcinogenicity.
• Limitations the authors state:
  • Mesotheliomas were not part of the primary analysis because carcinogenic effects at this site were relatively infrequent
  • Some chemicals missed by a reduced protocol may not have met the exposure and production criteria of the NTP Annual Report on Carcinogens, so their absence from that report may not reflect low hazard
  • Fewer than half of the chemicals missed or downgraded by a reduced protocol had been formally evaluated by IARC

Topics

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

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