Effect of Carcinogens and Analogs on Interferon Induction

Abstract

Pretreatment of mouse embryo fibroblasts with several chemicals, including 7,12-dimethylbenz-(α)-anthracene, 2-aminofluorene, aflatoxin B₁, benzo-(α)-pyrene, styrene oxide, and the No. 4 fraction of tobacco smoke condensate, resulted in severely reduced production of interferon when the cells were challenged with Newcastle disease virus. All of the above chemicals are proven or strongly suggested carcinogens. When the analogs methyl methanesulfonate, a potent carcinogen, and ethyl methanesulfonate, a weak carcinogen, were applied to cells, interferon induction was only inhibited by the methyl methanesulfonate. Therefore, carcinogens may directly inhibit the induction of interferon by Newcastle disease virus.

Kinetics of Inhibition of in vitro Interferon-Alpha/Beta Production after Benzo-(a)-Pyrene Exposure

“…Inhibition of IFN induction by pretreatment of cell cultures with carcinogens has been demonstrated by several laboratories [1][2][3][4][5][6][7]. Most previous studies have involved treatment of the cells with the carcinogen for 24 h, followed by IFN induction and 24 h further incubation before assaying culture supernatants for IFN activity [1,5.…”

“…6]. Poor or noncarcinogens had no significant effect on IFN induction [1][2][3][4][5][6][7]. Loss of via bility of the cells due to carcinogen treatment did not appear to play a major role in inhibition of IFN induction, as demonstrated by trypan blue viability staining and normal virus replication in carcinogentreated cells [1][2][3][4][5][6][7]; however, the question of changes in viability of carcinogen-treated cell cultures has not been completely ruled out.…”

“…Since the IFN assay was a biological assay and a titration, a two-fold change (50% decrease or 100% increase) in IFN titer that was statistically significant was required for a chemical treatment to be considered to have an effect [1], Inhibi tion of IFN induction after treatment with a car cinogen. BP.…”

“…Several workers have shown that pretreatment of cell cultures for 24 h with carcinogens resulted in in hibition of interferon(IFN)-alpha/beta induction in those cells [1][2][3][4][5][6][7]. Treatment of cells with poor or noncarcinogenic analogues had no effect on IFN induc tion [ 1 7], The carcinogen treatment did not apparent ly grossly affect cell viability, as shown by trypan blue viability staining, and by the normal replication of virus in carcinogen-treated cells [1.…”

“…Mouse L-929 cells were treated with dosages of BP known to inhibit IFN induction [1], IFN-alpha/beta was induced in the cells at the appropriate time inter val with polyriboinosinic-polyribocytidylic acid (poly-I-C). At least 24 h of incubation of the cells after initial addition of BP were required for IFN induction to be significantly inhibited; however, the physical presence of BP in the cell cultures was required for only 15 min.…”