Tumorigenic response in lung tumor susceptible A/J mice after sub-chronic exposure to calcium chromate or iron (III) oxide.

Abstract

Iron oxides are Group 3 (not classifiable as to its carcinogenicity to humans) according to the International Agency for Research on Cancer (IARC). Occupational exposures during iron and steel founding and hematite underground mining as well as other iron predominant exposures such as welding are Group 1 (carcinogenic to humans). The objective of this study was to investigate the potential of iron as iron (III) oxide (Fe2O3) to initiate lung tumors in A/J mice, a lung tumor susceptible strain. Male A/J mice were exposed by oropharyngeal aspiration to suspensions of Fe2O3 (1 mg) or calcium chromate (CaCrO4; 100 μg; positive control) for 26 weeks (once per week). Shams were exposed to 50 μL phosphate buffered saline (PBS; vehicle). Mice were euthanized 70 weeks after the first exposure and lung nodules were enumerated. Both CaCrO4 and Fe2O3 significantly increased gross-observed lung tumor multiplicity in A/J mice (9.63 ± 0.55 and 3.35 ± 0.30, respectively) compared to sham (2.31 ± 0.19). Histopathological analysis showed that bronchiolo-alveolar adenomas (BAA) and carcinomas (BAC) were the primary lung tumor types in all groups and were increased in the exposed groups compared to sham. BAC were significantly increased (146 %) in the CaCrO4 group and neared significance in the Fe2O3 group (100 % increase; p = 0.085). BAA and other histopathological indices of toxicity followed the same pattern with exposed groups increased compared to sham control. In conclusion, evidence from this study, in combination with our previous studies, demonstrate that exposure to iron alone may be a potential risk factor for lung carcinogenesis.

• Authors: Patti C Zeidler-Erdely, Lauryn M Falcone, James M Antonini, Kelly Fraser, Michael L Kashon, Lori A Battelli, Rebecca Salmen, Taylor Trainor, Lindsay Grose, Sherri Friend, Chengfeng Yang, Aaron Erdely
• Journal: Toxicology letters (Toxicol Lett) Vol. 334 Pg. 60-65 (Nov 01 2020) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 32961271 (Publication Type: Journal Article)
• Copyright: Published by Elsevier B.V.

Chemical References

• Air Pollutants, Occupational
• Calcium Compounds
• Chromates
• Ferric Compounds
• ferric oxide
• calcium chromate(VI)

Topics

• Air Pollutants, Occupational (toxicity)
• Animals
• Calcium Compounds (toxicity)
• Carcinogenesis (drug effects)
• Chromates (toxicity)
• Disease Susceptibility
• Dose-Response Relationship, Drug
• Ferric Compounds (toxicity)
• Hyperplasia (chemically induced, pathology)
• Lung (drug effects, pathology)
• Lung Neoplasms (chemically induced, pathology)
• Male
• Mice
• Mice, Inbred Strains
• Welding