Mutation Research, 289 (1993) 165-170 165 © 1993 Elsevier Science Publishers B.V. All rights reserved 0027-5107/93/$06.00 MUT 05272 The mutagenic effect of elevated temperatures in yeast is blocked by a previous heat shock Elia Nunes, E. Carmen Candreva, Deborah Keszenman and V. Alberto Salvo Department of Biophysics, Faculty of Medicine, Montevideo, Uruguay (Received 24 December 1992) (Revision received 29 March 1993) (Accepted 31 March 1993) Keywords: Hyperthermia; Heat shock; Yeast Summary We have analyzed the mutagenic effect of elevated temperatures (hyperthermia: HT) either upon direct exposure or after a previous heat shock (HS) in the haploid auxotrophic Saccharomyces cerevisiae strain SC7K lys2-3 in the logarithmic phase of growth. We demonstrated a significant antimutagenic effect of HS (38°C for 1 h) followed by hyperthermia (48°C, up to 60 min). Using cycloheximide (CHM) during the HS exposure we reversed the antimutagenic effect. We suggest that, upon HS, the enzymes involved in repair of premutational damage are more resistant to denaturation, i.e., by the induced HSP genes, and could work efficiently to prevent damage fixation in critical targets. CHM blocks the antimutagenic effect of the HS treatment by inhibiting the inducible synthesis of HSP. It is known that elevated temperatures can induce intra- and intermolecular bond disrup- tions producing reversible or irreversible changes in living systems (see Lindquist, 1986; Lindquist and Craig, 1988, for reviews). Furthermore, a transient and moderate elevation of the environ- mental temperature (HS: heat shock) can induce an increased resistance against heat (thermotoler- ance) or other damaging agents, such as ionizing and UV radiation (Plesset et al., 1987; Mitchel and Morrison, 1982, 1986, 1987). Thermotoler- ance seems to be a universal response and it has been recently associated with the regulated tran- Correspondence: Dr. E. Nunes, Facultad de Medicina, Dpt. Biofisica, LOB, Gral. Flores 2125, Montevideo, Uruguay. scription of a set of heat shock proteins (HSP). The highly conserved HSPI04 and HSP70 fami- lies seem to play a crucial role in the induced stress response (Sfinchez and Lindquist, 1990; Parsell et al., 1991; Boorstein and Craig, 1990). Several authors have described the potentially lethal effect of hyperthermia, which provides the basis for a type of tumor therapy (Overgaard, 1984, for review). Relatively few reports in the literature stressed the mutagenic effect of heat (Mueller, 1928; Zamenhof, 1960; Schenberg- Frascino and Moustacchi, 1972; Baltz et al., 1976; Bingham et al., 1976; Tanaka et al., 1989; Keszenman et al., 1991). In yeast cells, forward and petite mutations have been studied after exposure to hyperthermia (Sherman, 1958; Schenberg-Frascino and Moustacchi, 1972). Fur-