Multinucleate cells (MNC) as sensitive semiquantitative biomarkers of the toxic effect after experimental fibrous dust and cigarette smoke inhalation by rats.

Changes in the counts of binucleate (BNC) and multinucleate cells (MNC) in cell mixtures from lung tissue and bronchoalveolar lavage fluid (BALF) as well as in proportions of four types of BALF cells: Alveolar macrophages (AM), lymphocytes, polymorphonuclears (PMN), BNC and in total BALF protein were followed in a study comparing the toxicity of wollastonite with that of amosite asbestos in Fischer 344 rats. Both of the fibrous dusts were inhaled every second day at 30 or 60 mg/m3 air combined with daily exposure to cigarette smoke at 30 mg of total particulate matter (TPM)/m3 air for 1 h. The exposures lasted 175 days. Both, proportions of BNC as well as of MNC in lung cell mixtures rose significantly after exposure to cigarette smoke only. After inhalation of wollastonite the BNC proportions in all except the lower dust exposure group compared to controls showed a significant rise with the maximal factor value of 2.1 in the higher dust plus smoke exposure group. Wollastonite caused only marginal changes in MNC and other inflammation parameters. After inhalation of amosite at comparing to controls the proportion of BNC rose 8 times in the 30 mg/m3 and 11 times in the 60 mg/m3 exposure group, respectively. The effect of smoking was additive. The proportions of MNC were 39 times higher in the 30 mg/m3 and 41 times higher in the 60 mg/m3 amosite exposure group than in controls. In the higher exposure group the effect of smoking was synergic in that the MNC proportion rose about 58 times over control values from 0.05% up to about 3.0% (99% confidence interval--CI = 2.7-3.3%). The other followed inflammation parameters showed the presence of inflammation in the lung. It could be concluded that wollastonite at the same inhalation exposure concentration caused in rats less toxic effects than amosite, and, that the number of MNC, as well as BNC in lung cell mixtures and in BALF may serve as an important semiquantitative biomarker of inflammation.