Influence of mouse liver stored vitamin A on the induction of mutations (Ames tests) and SCE of bone marrow cells by aflatoxin B₁, benzo(a)pyrene, or cyclophosphamide

Abstract

Male mice (C57BL/6J) at 2 weeks of age were divided into two groups and maintained on a vitamin A-deficient or vitamin A-(retinyl acetate) supplemented diet. After 8 weeks, the average liver vitamin A concentration of mice fed on vitamin A-deficient or -supplemented diet was 36 +/- 7 micrograms/g vs 287 +/- 22 micrograms/g, respectively. Uninduced liver S9 fractions were prepared from both groups of mice and used to activate (with cofactors) the precarcinogens aflatoxin B1 (AFB), cyclophosphamide (CPP), dimethylbenz(a)anthracene (DMBA), and benzo(a)pyrene (BP) in the Salmonella mutagenicity assay. S9 fraction prepared from both groups of mice failed to activate CPP to metabolites mutagenic in tester strains TA100 and TA1535 or to activate DMBA to metabolites mutagenic in TA100, but effectively activated AFB and BP to metabolites mutagenic in TA98. Comparison of activation activities of S9 prepared from liver of mice fed a high or low level of vitamin A was made with T98 treated with AFB or BP using three doses of S9 (50, 100, and 200 microliters/plate). S9 fractions from mice with a high liver vitamin A level were consistently less potent than S9 fractions from mice with a low liver vitamin A level in activating AFB to its mutagenic metabolites. This effect was not observed in BP-treated plates. Administration of AFB to groups of mice with a high liver vitamin A level induced significantly less SCE in bone marrow cells than did administration of AFB to mice with a low liver vitamin A level. This differential sensitivity was not observed when the two groups of mice were treated with either BP or CPP. The possible relationship between vitamin A levels in vivo and mutagenesis or carcinogenesis are discussed briefly.

Antimutagenic activity of β-carotene

“…No such protective effect was observed in a preliminary experiment with benzo(a)pyrene (5 and 10 ~tg/dish), which is consistent with previous data [11]. The positive effect of BC in experiments with CP [1] (which requires an inductor of the microsomal enzyme system common to 2-acetylaminofluorene) implies its relationship with retinol [6] with respect to inhibitory effects against mutagens activated by certain forms of cytochrome P-450. Not one modification of the Ames test revealed an effect of BC on the mutagenicity of the three direct mutagens, which is in conformity with previous data [1,9].…”

“…The specificity of the effect of BC was found in cultured CHO cells: when added to the culture medium, it reliably lowered the level of CA induced by directly acting mutagens but was inactive against others [10]. Since little has been reported on the antimutagenic effect of BC, established [1,6,9] and not established [1,9,11] in the Ames test, it seemed important to study this effect using modeled gene mutations in microbial cells.…”

Evaluation of the mutagenicity of β‐myrcene in mammalian cells in vitro

“…Further studies have to show whether the antimutagenic activity of myrcene is also relevant for the in vivo situation. For vitamin A and dietary carrot it could be demonstrated that an antimutagenic effect also exists in vivo [Qin and Huang, 1986;Darroudi et al, 19881. However, administration of P-myrcene to rats did not result in any significant effect on the hepatic drug metabolizing enzymes and in particular no significant change in the amount of PB-P-450 was found [Madyastha and Srivatsan, 1987;Austin et al, 19881.…”

Aflatoxin B1 - Prevention of Its Genetic Damage by Means of Chemical Agents

“…The effects were determined in strains TA98 and TA100, where the authors considered that the observed capacity of the vitamin could be related with the inhibition of AFB1 metabolism or with an increased breakdown of the active metabolite (Busk & Ahlborg, 1980;Raina & Gurtoo, 1985). Other strains (TA102 and TA1535) were also tested and revealed positive results (Qin & Huang, 1986). In Chinese hamster V79 cells, (Huang et al, 1982) found a similar effect.…”