Gelderblom W C, Snyman S D, van der Westhuizen L, Marasas W F
Programe on Mycotoxins and Experimental Carcinogenesis, Tygerberg, South Africa.
Carcinogenesis. 1995 Mar;16(3):625-31. doi: 10.1093/carcin/16.3.625.
The inhibitory effect of fumonisin B1 (FB1) on epidermal growth factor (EGF)-induced DNA synthesis in primary rat hepatocytes was investigated by monitoring the incorporation of [3H]thymidine in the DNA. A pulse-labelling technique was adapted to determine the incorporation of the radioactivity in the DNA (S-phase) quantitatively. FB1 inhibits the EGF-induced DNA synthesis up to 90% when incorporated at concentrations of 150 to 300 microM for a period of 44 h. A continued presence of FB1 is required to exhibit this inhibition as (i) the subsequent removal of FB1 resulted in a reversal of the effect, (ii) a higher stimulatory response in EGF-treated hepatocytes was found when the exposure period of hepatocytes in FB1 was reduced, and (iii) pretreatment of hepatocytes with FB1 only slightly reduced (not significantly) DNA synthesis induced by EGF. Whilst the growth inhibitory effect of FB1 was not associated with a cytotoxic effect, binding studies using [125I]EGF indicated that the growth factor-receptor interaction was not altered. No relationship was found between the disruption of the sphingolipid biosynthesis by FB1 and (i) the mitoinhibitory effect on the EGF response and (ii) the cytotoxicity of FB1 in primary hepatocytes.
通过监测[3H]胸腺嘧啶核苷掺入DNA的情况，研究了伏马菌素B1（FB1）对原代大鼠肝细胞中表皮生长因子（EGF）诱导的DNA合成的抑制作用。采用脉冲标记技术定量测定放射性物质掺入DNA（S期）的情况。当FB1以150至300 microM的浓度掺入44小时时，其对EGF诱导的DNA合成的抑制率高达90%。需要持续存在FB1才能表现出这种抑制作用，因为（i）随后去除FB1会导致效应逆转，（ii）当肝细胞在FB1中的暴露时间缩短时，在EGF处理的肝细胞中发现更高的刺激反应，并且（iii）仅用FB1预处理肝细胞只会轻微降低（不显著）EGF诱导的DNA合成。虽然FB1的生长抑制作用与细胞毒性作用无关，但使用[125I]EGF的结合研究表明生长因子-受体相互作用未改变。未发现FB1对鞘脂生物合成的破坏与（i）对EGF反应的有丝分裂抑制作用和（ii）FB1在原代肝细胞中的细胞毒性之间存在关联。
