Effects of 3-aminobenzamide on the induction of morphologic transformation by diverse compounds in Balb/3T3 cells in vitro.
When cells were exposed simultaneously for a 24-h period to the poly(ADP-ribose) synthetase inhibitor 3-aminobenzamide (3AB) (1 or 3 mM) plus aflatoxin B1 (AfB1), no increase in toxicity and limited enhancement of transformation frequency (less than 2 X) was observed. Similarly, simultaneous treatment of cell with 3AB plus methylcholanthrene (MCA) had limited effects, slightly decreasing both toxicity and transformation. In contrast, simultaneous treatment with non-toxic doses of 3AB together with the alkylating agents N-methyl-N'-N-nitro-nitrosoguanidine (MNNG) or ethyl methanesulfonate (EMS) resulted in substantial enhancement of the toxicity and transforming effects of both short-chain alkylating agents. When EMS and varying doses of 3AB (0.1-3 mM) were administered simultaneously for 24 h, increasing levels of 3AB were found to cause a dose-dependent enhancement in toxicity and transformation. To explore the relationship of MNNG- and 3AB-induced effects, two further experiments were performed. First, cells were treated with MNNG plus 3AB for varying lengths of time (4, 24, 72 h). Although exposure for as little as 4 h enhanced toxicity and transformation, these effects were even more profound following 24 or 72 h exposure. Second, cells were exposed to 3AB for varing times prior to or after MNNG exposure. Under these conditions the addition of 3AB up to 6 h post MNNG exposure caused profound enhancement of toxicity and transformation, whereas addition of 3AB 24 h post exposure had minimal effects. Thus the co-carcinogenic effect of 3AB is agent-specific, time-specific and dose-dependent.
Lubet
R A
RA
McCarvill
J T
JT
Schwartz
J L
JL
Putman
D L
DL
Schechtman
L M
LM
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D002999:Clone Cells; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D007700:Kinetics; D008748:Methylcholanthrene / Q000633:toxicity; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C
D000348:Aflatoxins; D001549:Benzamides; D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D008748:Methylcholanthrene; C025160:3-aminobenzamide; D005020:Ethyl Methanesulfonate; D016604:Aflatoxin B1