Lack of Modifying Effects of Intratracheal Instillation of Quartz or Dextran Sulfate Sodium (DSS) in Drinking Water on Lung Tumor Development Initiated with 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Female A/J Mice

Abstract

The purpose of the present study was to investigate the effects of inflammation, induced by intratracheal instillation (i.t.) of quartz as an environmental factor in the lung or drinking of dextran sulfate sodium (DSS) as an environmental factor in the colon on lung tumors in female A/J mice initiated with NNK. For comparison, colonic preneoplastic lesions, aberrant crypt foci (ACF), were also assessed. A/J mice at 6 weeks of age were divided into 5 groups, and Groups 1, 2 and 3 were pretreated with NNK (2 mg / 0.1 ml saline / mouse, intraperitoneal injection) at week 0. For a week, 2% DSS in drinking water was administered to the mice in Groups 2 and 4 beginning in week 1. In week 2, the mice of Groups 3 and 5 were exposed to intratracheal instillation of quartz (0.1 mg/rat) suspended in 25 μl saline. The experiment was terminated after 16 weeks. The results for the lung tumors and colonic ACFs showed a lack of modifying effects of the inflammation in either site. Hematologically and histopathologically, the inflammation induced by 0.1 mg quartz in the lung and 2% DSS in the colon was lacking or only mild at the end of 16 weeks. These results suggest that there may be differences in sensitivity to inflammation that determine tumor promoting potential.

Keywords: A/J mouse; DSS; NNK; inflammation; lung tumor; quartz.

Fig. 1.

Experimental design. A total of 80 A/J mice, were divided into 5 groups at 6 weeks of age. Groups 1, 2 and 3 were pretreated with NNK (▲: 2 mg / 0.1 ml saline / mouse i.p.) in week 0. The mice of Groups 2 and 4 received 2% DSS (■) in drinking water for one week from week 1. In weeks 2, the mice of Groups 3 and 5 were exposed to intratracheal instillation of quartz (△: 0.1 mg/rat) suspended in 25 ml saline. The experiment was terminated after 16 weeks (S: sacrifice).

Fig. 2.

Histopathological findings for the lungs and colons of the A/J mice. A, Group 1 lung (magnification: × 20); B, Group 3 lung (× 20); C, Group 1 colon (× 100); D, Group 2 colon (× 100). Histopathologically, a change was only noted for intratracheal instillation of quartz in Group 3 (Fig. 2–B). DSS also induced only mild inflammatory changes in the colons of Group 2 (Fig. 2–D).