NASAL CAVITY DEPOSITION, HISTOPATHOLOGY, AND CELL-PROLIFERATION AFTER SINGLE OR REPEATED FORMALDEHYDE EXPOSURES IN B6C3F1 MICE AND F344 RATS
NASAL CAVITY DEPOSITION, HISTOPATHOLOGY, AND CELL-PROLIFERATION AFTER SINGLE OR REPEATED FORMALDEHYDE EXPOSURES IN B6C3F1 MICE AND F344 RATS
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DOI：
10.1016/0041-008x(83)90001-7
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发表时间：
1983-01-01
影响因子：
3.8
通讯作者：
BARROW, CS
中科院分区：
文献类型：
--
作者：
CHANG, JCF;GROSS, EA;BARROW, CS
吸入暴露于14.3 ppm甲醛（HCHO）2年诱导F-344大鼠鼻腔鳞状细胞癌的发病率为50%，而B6 C3 F1小鼠的发病率仅为3.3%。由于反应具有浓度和种属依赖性，因此将鼻腔剂量的种属差异作为肿瘤发生率差异的可能机制进行了检查。将未经处理的（未预处理的）和HCHO预处理的小鼠和大鼠暴露于HCHO 6小时，在此期间记录呼吸速率和潮气量以计算HCHO在鼻上皮上的理论沉积（μ g/min/cm 2）。通过比较放射自显影、组织病理学和细胞更新研究进一步评估了递送剂量的种属差异。由于小鼠在重复暴露后能够更好地减少每分钟通气量，因此它们比大鼠具有更少的可用于沉积的HCHO，从而导致更少的组织损伤和更低的鼻上皮细胞更新率。计算的剂量和观察到的鼻毒性（包括鼻肿瘤发生率）之间的相关性表明，通过将剂量测定标准化为鼻表面积，可以更好地理解鼻毒性的种属差异。
Inhalation exposure for 2 yr to 14.3 ppm formaldehyde (HCHO) induced a 50% incidence of squamous cell carcinoma in the nasal cavity of F-344 rats but only a 3.3% incidence in B6C3F1 mice. Since the response was concentration and species dependent, species differences in nasal cavity dose were examined as a possible mechanism for the differences in tumor incidence. Naive (nonpretreated) and HCHO-pretreated mice and rats were exposed to HCHO for 6 h during which respiratory rate and tidal volume were recorded to calculate the theoretical deposition (.mu.g/min per cm2) of HCHO on the nasal epithelium. Species differences in delivered dose were further assessed by comparative autoradiography, histopathology, and cell turnover studies. Because mice were better able to reduce minute ventilation upon repeated exposures, they had less HCHO available for deposition than rats, resulting in less tissue damage and a lower rate of cell turnover in the nasal epithelium. The correlation between calculated dose and observed nasal toxicity, including nasal tumor incidence, demonstrates that by normalizing the dosimetry to nasal surface area, species differences in nasal toxicity may be better understood.