Mitsui-7 MWCNTs are strong lung tumor promoters in B6C3F1 mice. B6C3F1 mouse lung tumors have many molecular and morphological similarities to human pulmonary tumors. In previous work, we have demonstrated that exposure to inhaled Mitsui-7 following exposure to a DNA damaging agent caused potent promotion of lung tumors. To investigate a possible threshold for Mitsui-7-induced carcinogenesis, we exposed B6C3F1 mice to a single dose of either methylcholanthrene (MC, 10 microg/g BW, i.p.) or vehicle (corn oil). One week after i.p. injections, mice were exposed by inhalation to MWCNTs (5 mg/m3, 5 hours/day, 5 days/week) or filtered air (controls) for a total of 2, 5 or 10 days. At 17 months post-exposure, mice were euthanized and examined for lung tumor formation. Thirty six percent of the filtered air controls, 33% of the MWCNT-exposed, and 47% of the MC-exposed, had a mean of 0.33, 0.33 and 0.4 tumors per mouse, respectively. By contrast, 94% of the mice which received MC followed by 10 days MWCNT had an average of 2.9 tumors per mouse while 81% of the mice exposed to 5 days of MWCNTs had 1.9 tumors per mouse, and 73% of the mice exposed to 2 days of MWCNTs had 1.2 tumors per mouse. Additionally, mice exposed to MWCNTs or MC followed by MWCNTs had larger tumor volumes than their corresponding air-exposed control groups. Preliminary data indicate a dose response in the percent of animals with tumors as well as the number of tumors per animal following exposure to MC and MWCNTs. In this study, mouse MWCNT lung burden approximates feasible human occupational exposures.
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