PMID- 3033490 OWN - NLM STAT- MEDLINE DCOM- 19870617 LR - 20190702 IS - 0027-5107 (Print) IS - 0027-5107 (Linking) VI - 183 IP - 3 DP - 1987 May TI - Nitropyrenes are inducers of polyoma viral DNA synthesis. PG - 203-11 AB - The biological activity of a series of nitropyrenes was assayed by measuring their ability to induce the asynchronous replication of viral DNA in rat fibroblasts transformed by a ts-a mutant of polyoma virus. Concentrations of 10-30 micrograms/ml of 1-nitropyrene (1-NP) induced viral replication, and this effect was enhanced by addition of rat-liver S9 microsomal fraction (300 micrograms/ml) to the culture medium. The response was less than that obtained with 0.1 micrograms/ml of the activated metabolite of benzo[a]pyrene (BP), BP trans-7,8-dihydrodiol-9,10 epoxide (anti) (BPDE). A series of di-, tri-, and tetra-nitropyrenes were also found to induce polyoma DNA replication, in the absence of exogenous microsomal activation, displaying strongly positive effects at 0.5-2.0 microgram/ml. Dose-response curves with 1,6-dinitropyrene (1,6-DNP) from 0.01 to 0.5 microgram/ml indicated that this compound was approximately equipotent with BPDE for induction of polyoma DNA synthesis. Studies of drug metabolism, DNA binding and DNA adduct formation indicate that 1,6-DNP is metabolized in this cell line, binds to DNA, and forms stable adducts. The level of DNA modification seen with 1,6-DNP is higher than that observed under comparable conditions with an equivalent dose of BPDE. These findings provide additional evidence that the nitropyrene class of compounds can exert biological effects in mammalian cells, and that the dinitropyrenes are more potent than 1-NP. FAU - Lambert, M E AU - Lambert ME FAU - Weinstein, I B AU - Weinstein IB LA - eng GR - CA0211/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Mutat Res JT - Mutation research JID - 0400763 RN - 0 (DNA, Viral) RN - 0 (Pyrenes) RN - 3417WMA06D (Benzo(a)pyrene) RN - 55097-80-8 (7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide) RN - 66Q2ZUF83N (1,6-dinitropyrene) SB - IM MH - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/metabolism MH - Animals MH - Benzo(a)pyrene/metabolism/pharmacology MH - Biotransformation MH - Cell Line MH - *DNA Damage MH - DNA, Viral/*biosynthesis MH - Polyomavirus/drug effects/*genetics MH - Pyrenes/metabolism/*pharmacology MH - Rats MH - Structure-Activity Relationship MH - Virus Replication/drug effects EDAT- 1987/05/01 00:00 MHDA- 1987/05/01 00:01 CRDT- 1987/05/01 00:00 PHST- 1987/05/01 00:00 [pubmed] PHST- 1987/05/01 00:01 [medline] PHST- 1987/05/01 00:00 [entrez] AID - 0167-8817(87)90001-0 [pii] AID - 10.1016/0167-8817(87)90001-0 [doi] PST - ppublish SO - Mutat Res. 1987 May;183(3):203-11. doi: 10.1016/0167-8817(87)90001-0.