Hyperplastic and neoplastic changes in the lungs of rats treated concurrently with chrysotile asbestos and N-nitrosoheptamethyleneimine

This study investigated the combined effect in rat lungs of simultaneous ex posure to chrysotile asbestos and N-nitrosoheptamethyleneimine (NHMI), with the objective of determining the potential for chrysotile to promote or ot herwise enhance the pathological responses to this potent rodent lung carci nogen. Groups of 15 or 20 male and female animals were treated with 0, 3, o r 70 mg kg(-1) NHMI subcutaneously once a week for 10 wk, plus either clean air (control) or 50 mg m(-3) chrysotile by nose-only inhalation for 4 wk. A broad range of pulmonary metaplastic, hyperplastic, and neoplastic lesion s was observed. Effects were more marked in male than in female animals. NH MI treatment increased the incidence of hyperplastic lesions, with apparent augmentation by chrysotile exposure (not statistically significant). Simii arly, a "promoting" effect of chrysotile in the induction of lung tumors wa s observed, with all but 2 of the 11 primary tumors detected being in anima ls treated with both NHMI and asbestos. However, this apparent interaction was again not confirmable statistically probably because of the low number of observed tumors (stemming from premature termination of the experiment). The study results are in line with those of similar previous studies, whic h found a higher incidence of hyperplastic and neoplastic changes in animal s treated with both nitrosamine and asbestos than in those given nitrosamin e alone. It is proposed that the method described (with minor modification) could be used to investigate either (1) the ability of other inhaled parti cles to augment NHMI carcinogenicity, or (2) the propensity of other chemic al carcinogens to interact with asbestos in the production of pulmonary neo plasms.