目的探讨ｐ５３基因与化学致癌剂诱发小鼠皮肤肿瘤的关系。方法运用ＰＣＲＳＳＣＰ和直接ＤＮＡ测序法，检测３７例ＤＭＢＡＴＰＡＭＮＮＧ诱发的小鼠皮肤肿瘤［包括６例乳头状瘤，１５例高分化鳞状细胞癌（ＳＣＣＩ）和１６例中分化鳞状细胞癌（ＳＣＣⅡ）］中，ｐ５３基因第５～８外显子的序列改变。结果乳头状瘤均未见ｐ５３基因突变，而２５８％（８／３１例）ＳＣＣ测得突变，其中ＳＣＣⅠ和ＳＣＣⅡ突变率分别为２６６％（４／１５例）和２５％（４／１６例）。在这８例肿瘤中共有９个突变，其中７个位于第８外显子，有７个为Ｇ→Ａ转换。结论ｐ５３基因突变发生于该三步化学致癌法诱发的小鼠皮肤乳头状瘤向ＳＣＣ恶性转化过程中。 Objective To investigate the relationship between p53 gene and chemical carcinogen-induced mouse skin tumors. METHODS: PCR-SSCP and direct DNA sequencing were used to detect 37 mouse skin tumors induced by DMBA-TPA-MNNG [including 6 papillomas, 15 well-differentiated squamous cell carcinomas (SCCI) and 16 moderately differentiated squamous cell carcinomas. In squamous cell carcinoma (SCCII)], the sequence of exon 5-8 of the p53 gene changes. Results No mutations in p53 gene were detected in papilloma and mutations were detected in 258% (8/31 cases) of SCC. The mutation rates of SCCI and SCCII were 266% (4/15 cases) and 25% (4) respectively. /16 cases). There were 9 mutations in these 8 tumors, of which 7 were in exon 8 and 7 were G → A transitions. Conclusion The p53 gene mutation occurs in the three-step chemical carcinogenesis-induced mouse skin papilloma to malignant transformation of SCC.