Effects of O6-benzylguanine on growth and differentiation of P19 embryonic carcinoma cells treated with alkylating agents

Seeley, Marguerite R.; Faustman, Elaine M.

doi:10.1002/(sici)1520-6866(1998)18:3<111::aid-tcm2>3.0.co;2-j

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“…In our laboratories, various cells were routinely maintained at 10 µM BG, and no such effect was seen (unpublished results). A study using P19 embryonic carcinoma cells has shown that their growth and differentiation is not affected by BG at concentrations of 5 and 10 µM whereas slight effects were seen (decrease of <5% of control) at concentrations of 25 µM; significant effects were seen only at 100 µM of BG (35).…”

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confidence: 99%

O⁶-3-[¹³¹I]iodobenzylguanine: Improved Synthesis and Further Evaluation of a Potential Agent for Imaging of Alkylguanine-DNA Alkyltransferase

et al. 2004

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O(6)-Benzylguanine derivatives with suitable radionuclides attached to the benzyl ring are potentially useful in the noninvasive imaging of the DNA repair protein, alkylguanine-DNA alkyltransferase (AGT). Previously, O(6)-3-[(131)I]iodobenzylguanine ([(131)I]IBG) was prepared using a two-step approach; we now report its synthesis in a single step by the radioiododestannylation of O(6)-3-(trimethylstannyl)benzylguanine in 85-95% radiochemical yield. The in vitro specific uptake of [(131)I]IBG in DAOY human medulloblastoma cells, in TE-671 human rhabdomyosarcoma cells and a CHO cell line transfected to express AGT was linear (r(2) = 0.9-1.0) as a function of cell density. After intravenous injection of [(131)I]IBG in athymic mice bearing TE-671 xenografts, tumor uptake was 1.38 +/- 0.34% ID/g at 0.5 h and declined at 2 and 4 h. Preadministration of O(6)-(3-iodobenzyl)guanine (IBG) at 0.5 h increased uptake not only in tumor but also in several normal tissues. Notable exceptions were thyroid (p < 0.05), lung (p <0.05) and stomach. After intratumoral injection of [(131)I]IBG in the same xenograft model, the uptake in tumors that were depleted of AGT by BG treatment (165.8 +/- 27.5% ID/g) was about 60% of that in control mice (272.4 +/- 48.2% ID/g; p < 0.05).

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Section: Resultsmentioning

confidence: 99%

O⁶-3-[¹³¹I]iodobenzylguanine: Improved Synthesis and Further Evaluation of a Potential Agent for Imaging of Alkylguanine-DNA Alkyltransferase

et al. 2004

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Effects of O6-benzylguanine on growth and differentiation of P19 embryonic carcinoma cells treated with alkylating agents

Cited by 1 publication

References 22 publications

O⁶-3-[¹³¹I]iodobenzylguanine: Improved Synthesis and Further Evaluation of a Potential Agent for Imaging of Alkylguanine-DNA Alkyltransferase

O⁶-3-[¹³¹I]iodobenzylguanine: Improved Synthesis and Further Evaluation of a Potential Agent for Imaging of Alkylguanine-DNA Alkyltransferase

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Effects of O6-benzylguanine on growth and differentiation of P19 embryonic carcinoma cells treated with alkylating agents

Cited by 1 publication

References 22 publications

O6-3-[131I]iodobenzylguanine: Improved Synthesis and Further Evaluation of a Potential Agent for Imaging of Alkylguanine-DNA Alkyltransferase

O6-3-[131I]iodobenzylguanine: Improved Synthesis and Further Evaluation of a Potential Agent for Imaging of Alkylguanine-DNA Alkyltransferase

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O⁶-3-[¹³¹I]iodobenzylguanine: Improved Synthesis and Further Evaluation of a Potential Agent for Imaging of Alkylguanine-DNA Alkyltransferase

O⁶-3-[¹³¹I]iodobenzylguanine: Improved Synthesis and Further Evaluation of a Potential Agent for Imaging of Alkylguanine-DNA Alkyltransferase