Galloway S M, Sofuni T, Shelby M D, Thilagar A, Kumaroo V, Kaur P, Gulati D, Putman D L, Murli H, Marshall R, Tanaka N, Anderson B, Zeiger E, Ishidate M
Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Environ Mol Mutagen. 1997;29(2):189-207.
Different test results have been reported for the same chemicals in two in vitro chromosome aberration test systems, CHL cells tested by a Japanese protocol and CHO cells tested by the US National Toxicology Program [Sofuni et al., Mutat Res 241:173-213,1990]. Here, laboratories in Japan, the US and the UK tested 9 such chemicals in CHL and CHO cells using the same protocols and found all 9 positive in both cell types; differences in earlier conclusions with these chemicals were due mainly to test protocol, not to different sensitivities of the cells. The most important protocol difference is sampling time. Chemicals that were negative in the NTP series using a sampling time of 10 to 13 hours often produced positive results when retested here with a 20- to 24-hour sampling time. While positive results were obtained in both cell types, CHL cells sometimes had higher aberration levels and survived at higher doses than CHO cells would tolerate. This may reflect some intrinsic difference in sensitivity but may also be affected by factors such as cell cycle length and culture media (e.g., oxygen scavenging capacity). The collaboration reported here also contributed to a better understanding of scoring aberrations, especially "gaps"; there was good agreement on what types of aberrations should be included in the totals when scoring criteria were clearly defined, for example, many changes classified as "gaps" by the Japanese system were classified as "breaks" in the scoring systems used in the United States and the United Kingdom, and were appropriately included in total aberration counts.
对于两种体外染色体畸变测试系统中的相同化学物质，已报道了不同的测试结果，一种是按照日本方案测试的CHL细胞，另一种是按照美国国家毒理学计划测试的CHO细胞[索富尼等人，《突变研究》241:173 - 213，1990]。在此，日本、美国和英国的实验室使用相同方案在CHL和CHO细胞中测试了9种此类化学物质，发现这9种化学物质在两种细胞类型中均呈阳性；早期关于这些化学物质的结论差异主要归因于测试方案，而非细胞的不同敏感性。最重要的方案差异是取样时间。在国家毒理学计划系列中，取样时间为10至13小时呈阴性的化学物质，当在此处采用20至24小时取样时间重新测试时，往往会产生阳性结果。虽然在两种细胞类型中均获得了阳性结果，但CHL细胞有时畸变水平更高，并且在比CHO细胞所能耐受的更高剂量下存活。这可能反映了敏感性方面的一些内在差异，但也可能受到细胞周期长度和培养基等因素的影响（例如，氧清除能力）。此处报道的合作也有助于更好地理解对畸变进行评分，尤其是“裂隙”；当评分标准明确界定后，对于在计算总数时应包括哪些类型的畸变达成了良好共识，例如，日本系统归类为“裂隙”的许多变化在美国和英国使用的评分系统中被归类为“断裂”，并被适当地纳入总畸变计数中。
